Kumar N

References (40)

Title : Effect of naringin on sodium fluorideinduced neurobehavioral deficits in Wistar rats - Swamy_2024_Biomed.Rep_20_97
Author(s) : Swamy RS , Kumar N , Shenoy S , Rao V
Ref : Biomed Rep , 20 :97 , 2024
Abstract : There is a lack of treatment for the detrimental effects of fluorosis. Sodium fluoride at a concentration of 10 ppm induces stress, depression and memory impairment in adult Wistar rats. Naringin, a flavanone glycoside isolated from citrus fruits such as lemons and oranges, possesses anti-inflammatory, antioxidant and neuroprotective properties; therefore, it was used for treatment of fluoride induced toxicity in the present study. Adult Wistar rats were divided into eight groups (n=8). The normal control (NOR) group was provided with normal tap water. The sodium fluoride (FLU)10 group received water containing 10 ppm sodium fluoride for 60 days. The treatment groups (FLU10NAR100 and FLU10NAR50) received drinking water with 10 ppm sodium fluoride ad libitum along with Naringin 100 and 50 mg/kg body weight (bw) per oral gavage, respectively. The NAR100 and NAR50 groups received Naringin 100 and 50 mg/kg bw. The PRONAR100 and PRONAR50 groups received Naringin 100 and 50 mg/kg bw for the first 15 days and then subsequently received FLU10 ppm for 60 days (total of 75 days). All animals were subjected to behavioural tests consisting of the open field test (OFT), forced swim test (FST) and novel object recognition test (NORT). After euthanasia, the hippocampus and prefrontal cortex were stained with Cresyl violet. To measure the oxidative stress caused by fluoride and its effect on antioxidant levels, estimation of reduced glutathione (GSH) by Ellman's method, lipid peroxidation (LPO) measured in terms of the MDA:thiobarbituric acid reaction and catalase was performed. To evaluate the effect of fluoride on activity of acetylcholine, estimation of acetylcholinesterase (AChE) by Ellman's method was performed. In NORT and FST, significant changes (P<0.05) were present in the FLU10NAR100 and FLU10NAR50 groups compared with the FLU10 group, showing recovery from memory deficit and depression. The OFT results were insignificant. The LPO was reduced in all the other groups except the FLU10 group, with statistically significant changes. Catalase activity was significantly lower in FLU10 as compared with the NAR100, NAR50, PRONAR100 and PRONAR50 groups. GSH and AChE activities did not show significant changes as compared with the FLU10 group. The CA3 and prefrontal cortex viable and degenerated neuron count in the FLU10 group were insignificant compared with all other groups, except for the NAR100 and NAR50 groups. Thus, Naringin can be a useful drug to avoid the neurological effects of fluoride.
ESTHER : Swamy_2024_Biomed.Rep_20_97
PubMedSearch : Swamy_2024_Biomed.Rep_20_97
PubMedID: 38765862

Title : Development of new benzil-hydrazone derivatives as anticholinesterase inhibitors: synthesis, X-ray analysis, DFT study and in vitro\/in silico evaluation - Tabbiche_2024_J.Biomol.Struct.Dyn__1
Author(s) : Tabbiche A , Bouchama A , Fadli K , Ahmad B , Kumar N , Chiter C , Yahiaoui M , Zaidi F , Boudjemaa K , Dege N , Djedouani A , Chafai N
Ref : J Biomol Struct Dyn , :1 , 2024
Abstract : Alzheimer's disease (AD) is a complex neurodegenerative disorder affecting the central nervous system. Current drugs for AD have limited effectiveness and often come with side effects. Consequently, there is a pressing need to develop new, safe, and more effective treatments for Alzheimer's disease. In this work, two novel benzil-hydrazone compounds, abbreviated 2-ClMHB and 2-ClBHB, were synthesized for the first time by refluxing the benzil with 2-Chloro phenyl hydrazine and they have been tested for their in vitro anti-cholinesterase activities and in silico acetyl and butyryl enzymes inhibition. The resulting products were characterized using UV-Vis and IR spectroscopy, while the single-crystal X-ray diffraction investigation was successful in establishing the structures of these compounds. DFT calculations have been successfully made to correlate the experimental data. According to biological studies, the synthesized hydrazones significantly inhibited both butyrylcholinesterase (2-ClMHB: 20.95 +/- 1.29 microM and 2-ClBHB: 31.21 +/- 1.50 microM) and acetylcholinesterase (2-ClMHB: 21.80 +/- 1.10 microM and 2-ClBHB: 10.38 +/- 1.27 microM). Moreover, molecular docking was also employed to locate the molecule with the optimum interaction and stability as well as to explain the experimental findings. The compound's dynamic nature, binding interaction, and protein-ligand stability were investigated using molecular dynamics (MD) simulations. Analyzing parameters such as RMSD and RMSF indicated that the compound remained stable throughout the 100 ns MD simulation. Finally, the drugs displayed high oral bioavailability, as per projected ADME and pharmacokinetic parameters.Communicated by Ramaswamy H. Sarma.
ESTHER : Tabbiche_2024_J.Biomol.Struct.Dyn__1
PubMedSearch : Tabbiche_2024_J.Biomol.Struct.Dyn__1
PubMedID: 38193889

Title : In Vitro and In Vivo Investigations of Chromone Derivatives as Potential Multitarget-Directed Ligands: Cognitive Amelioration Utilizing a Scopolamine-Induced Zebrafish Model - Kumar_2024_ACS.Chem.Neurosci__
Author(s) : Kumar N , Jangid K , Kumar V , Yadav RP , Mishra J , Upadhayay S , Devi B , Dwivedi AR , Kumar P , Baranwal S , Bhatti JS
Ref : ACS Chem Neurosci , : , 2024
Abstract : Alzheimer's disease is a complex neurological disorder linked with multiple pathological hallmarks. The interrelation of therapeutic targets assists in the enhancement of cognitive decline through interference with overall neuronal transmission. We have synthesized and screened various chromone derivatives as potential multitarget-directed ligands for the effective treatment of Alzheimer's disease. The synthesized compounds exhibited multipotent activity against AChE, BuChE, MAO-B, and amyloid beta aggregation. Three potent compounds, i.e., VN-3, VN-14, and VN-19 were identified that displayed remarkable activities against different targets. These compounds displayed IC(50) values of 80 nM, 2.52 microM, and 140 nM against the AChE enzyme, respectively, and IC(50) values of 2.07 microM, 70 nM, and 450 nM against the MAO-B isoform, respectively. VN-3 displayed potent activity against self-induced Abeta(1-42) aggregation with inhibition of 58.3%. In the ROS inhibition studies, the most potent compounds reduced the intracellular ROS levels up to 80% in SH-SY5Y cells at 25 microM concentration. The compounds were found to be neuroprotective and noncytotoxic even at a concentration of 25 microM against SH-SY5Y cells. In silico studies showed that the compounds were nicely accommodated in the active sites of the receptors along with thermodynamically stable orientations. Compound VN-19 exhibited a balanced multitargeting profile against AChE, BuChE, MAO-B, and Abeta(1-42) enzymes and was further evaluated for in vivo activities on the scopolamine-induced zebrafish model. VN-19 was found to ameliorate the cognitive decline in zebrafish brains by protecting them against scopolamine-induced neurodegeneration. Thus, VN-3, VN-14, and VN-19 were identified as potent multitarget-directed ligands with a balanced activity profile against different targets and can be developed as therapeutics for AD.
ESTHER : Kumar_2024_ACS.Chem.Neurosci__
PubMedSearch : Kumar_2024_ACS.Chem.Neurosci__
PubMedID: 38795037

Title : 3D-QSAR-based pharmacophore modelling of quinazoline derivatives for the identification of acetylcholinesterase inhibitors through virtual screening, molecular docking, molecular dynamics and DFT studies - Kumar_2024_J.Biomol.Struct.Dyn__1
Author(s) : Kumar V , Jangid K , Kumar N
Ref : J Biomol Struct Dyn , :1 , 2024
Abstract : Alzheimer's disease (AD) is a progressive neurological disorder responsible for the cognitive dysfunction and cognitive impairment in the patients. Acetylcholinesterase inhibitors (AChEIs) are used to treat AD however, these only provided symptomatic relief and more efficient drug molecules are desired for the effective treatment of the disease. In this article, ligand-based drug-designing strategy was used to develop and validate a field-based 3D-QSAR pharmacophore model on quinazoline-based AChEIs reported in the literature. The validated pharmacophore model (AAAHR_1) was used as a prefilter to screen an ASINEX database via virtual screening workflow (VSW). The hits generated were subjected to MM-GBSA to identify potential AChEIs and top three scoring molecules (BAS 05264565, LEG 12727144 and SYN 22339886) were evaluated for thermodynamic stability at the target site using molecular dynamic simulations. Additionally, DFT study was performed to predict the reactivity of lead molecules towards acetylcholinesterase (AChE). Thus, by utilising various computational tools, three molecules were identified as potent AChEIs that can be developed as potential drug candidates for the treatment of AD.Communicated by Ramaswamy H. Sarma.
ESTHER : Kumar_2024_J.Biomol.Struct.Dyn__1
PubMedSearch : Kumar_2024_J.Biomol.Struct.Dyn__1
PubMedID: 38329085

Title : Carbamate as a potential anti-Alzheimer's pharmacophore: A review - Singh_2023_Drug.Dev.Res__2
Author(s) : Singh YP , Kumar N , Chauhan BS , Garg P
Ref : Drug Dev Res , : , 2023
Abstract : Alzheimer's disease (AD) is a progressive age-related neurodegenerative brain disorder, which leads to loss of memory and other cognitive dysfunction. The underlying mechanisms of AD pathogenesis are very complex and still not fully explored. Cholinergic neuronal loss, accumulation of amyloid plaque, metal ions dyshomeostasis, tau hyperphosphorylation, oxidative stress, neuroinflammation, and mitochondrial dysfunction are major hallmarks of AD. The current treatment options for AD are acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and NMDA receptor antagonists (memantine). These FDA-approved drugs mainly provide symptomatic relief without addressing the pathological aspects of disease progression. So, there is an urgent need for novel drug development that not only addresses the basic mechanisms of the disease but also shows the neuroprotective property. Various research groups across the globe are working on the development of multifunctional agents for AD amelioration using different core scaffolds for their design, and carbamate is among them. Rivastigmine was the first carbamate drug investigated for AD management. The carbamate fragment, a core scaffold of rivastigmine, act as a potential inhibitor of acetylcholinesterase. In this review, we summarize the last 10 years of research conducted on the modification of carbamate with different substituents which primarily target ChE inhibition, reduce oxidative stress, and modulate Abeta aggregation.
ESTHER : Singh_2023_Drug.Dev.Res__2
PubMedSearch : Singh_2023_Drug.Dev.Res__2
PubMedID: 37694498

Title : Neuroprotective activity of novel phenanthrene derivative from Grewia tiliaefolia by in vitro and in silico studies - Rajput_2023_Sci.Rep_13_2444
Author(s) : Rajput A , Sharma P , Kumar N , Kaur S , Arora S
Ref : Sci Rep , 13 :2444 , 2023
Abstract : Medicinal plants possess range of phytochemicals accountable for their diverse biological activities. Presently, such compounds have been isolated from medicinal plants, characterized and evaluated for their pharmacological potential. In the present study, the efforts have been made to isolate the compound(s) from Grewia tiliaefolia Vahl., plant known for its ameliorative effect on brain related diseases such as anxiety, depression, cognitive disorders and Parkinson's disease. Plant extract was subjected to isolation of compound(s) using column chromatography and isolated compound was characterized by NMR FTIR and LCMS. The isolated compound was novel with the IUPAC name of the compound is propyl 3-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylate, designated as A-1 and has not been reported before. A-1 was further evaluated for its antioxidant potential using in vitro antioxidant assays (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH assay and reducing power assay, RPA). Also, Acetylcholinesterase (AChE) inhibitory potential of A-1 and extract was analysed. Results showed that A-1 exhibited significantly higher antioxidant activity in both DPPH and RPA assay as compared to plant extract. In case of AChE inhibitory activity again, A-1 has shown significantly higher activity as compared to plant extract. In silico study was conducted to predict its action on proteins playing crucial role in neurological and neurodegenerative disorders such as gamma amino butyric acid (GABA) receptor and glutamate alpha amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu AMPA) receptor in epilepsy and AChE enzyme in Alzheimer's diseases. The compound has shown interaction in following order: AChE > GABA receptor > Glu AMPA receptor. Further, molecular dynamic simulations and ADME studies of A-1 and AChE enzyme revealed that A-1 yielded good results in all parameters and hence can relieve Alzheimer's like symptoms.
ESTHER : Rajput_2023_Sci.Rep_13_2444
PubMedSearch : Rajput_2023_Sci.Rep_13_2444
PubMedID: 36765125

Title : Copper and nanocopper toxicity using integrated biomarker response in Pangasianodon hypophthalmus - Kumar_2023_Environ.Toxicol__
Author(s) : Kumar N , Gismondi E , Reddy KS
Ref : Environ Toxicol , : , 2023
Abstract : The current study focused on assessing the toxicological effects of copper (Cu) and copper nanoparticles (Cu-NPs) in acute condition on Pangasianodon hypophthalmus. The median lethal concentration (LC(50) ) for Cu and Cu-NPs were determined as 8.04 and 3.85 mg L(-1) , respectively. For the subsequent definitive test, varying concentrations were selected: 7.0, 7.5, 8.0, 8.5, and 9.0 mg L(-1) for Cu, and 3.0, 3.3, 3.6, 3.9, and 4.2 mg L(-1) for Cu-NPs. To encompass these concentration levels and assess their toxic effects, biomarkers associated with toxicological studies like oxidative stress, neurotransmission, and cellular metabolism were measured in the liver, kidney, and gill tissues. Notably, during the acute test, the activities of catalase, superoxide dismutase, glutathione-s-transferase, glutathione peroxidase, and lipid peroxide in the liver, gill, and kidney tissues were significantly increased due to exposure to Cu and Cu-NPs. Similarly, acetylcholinesterase activity in the brain was notably inhibited in the presence of Cu and Cu-NPs when compared to the control group. Cellular metabolic stress was greatly influenced by the exposure to Cu and Cu-NPs, evident from the considerable elevation of cortisol, HSP 70, and blood glucose levels in the treated groups. Furthermore, integrated biomarker response, genotoxicity, DNA damage in gill tissue, karyotyping in kidney tissue, and histopathology in gill and liver were investigated, revealing tissue damage attributed to exposure to Cu and Cu-NPs. In conclusion, this study determined that elevated concentrations of essential trace elements, namely Cu and Cu-NPs, induce toxicity and disrupt cellular metabolic activities in fish.
ESTHER : Kumar_2023_Environ.Toxicol__
PubMedSearch : Kumar_2023_Environ.Toxicol__
PubMedID: 38009665

Title : Donepezil-Inspired Multitargeting Indanone Derivatives as Effective Anti-Alzheimer's Agents - Singh_2022_ACS.Chem.Neurosci__
Author(s) : Singh JV , Thakur S , Kumar N , Singh H , Mithu VS , Bhagat K , Gulati HK , Sharma A , Sharma S , Bedi PMS
Ref : ACS Chem Neurosci , : , 2022
Abstract : In continuous efforts to develop anti-Alzheimer's agents, we rationally designed and synthesized a series of multitargeting molecules by incorporating the essential molecular features of the standard drug donepezil. Among the series, compound 4b showed multitargeting properties to act as an anti-Alzheimer's agent, which is better tolerable in vivo than donepezil. Acetylcholinesterase (AChE) inhibition data showed that compound 4b inhibits the enzyme with a half-maximal inhibitory concentration (IC(50)) value of 0.78 microM and also showed DNA protection, which was confirmed through the DNA nicking assay, suggesting the protective effect of 4b against oxidative DNA damage. Compound 4b also showed 53.04% inhibition against Abeta(1-42) aggregations, which was found comparable to that of the standard compound curcumin. Molecular dynamics simulations were performed to check the stability of compound 4b with the enzyme AChE, which showed that the enzyme-ligand complex is stable enough to block the hydrolysis of acetylcholine in the brain. Its higher LD(50) cutoff value (50 mg/kg) in comparison to donepezil (LD(50): 25 mg/kg) made it safer, suggesting that it can be used in further clinical experiments. To evaluate its anti-Alzheimer property, a mice model with melamine-induced cognitive dysfunction was used, and Morris water maze and Rotarod tests were performed. A significant improvement in memory was observed after the treatment with compound 4b and donepezil. The study postulated that the introduction of important structural features of donepezil (dimethoxyindanone moiety as ring-A) embarked with terminal aromatic ether (ring-B and ring-C) made 4b a multitargeting molecule that offers a way for developing alternative therapeutics in the future against Alzheimer's disease (AD).
ESTHER : Singh_2022_ACS.Chem.Neurosci__
PubMedSearch : Singh_2022_ACS.Chem.Neurosci__
PubMedID: 35195392

Title : Advancements in the development of multi-target directed ligands for the treatment of Alzheimer's disease - Kumar_2022_Bioorg.Med.Chem_61_116742
Author(s) : Kumar N , Kumar V , Anand P , Ranjan Dwivedi A
Ref : Bioorganic & Medicinal Chemistry , 61 :116742 , 2022
Abstract : Alzheimer's disease (AD) is a multifactorial irreversible neurological disorder which results in cognitive impairment, loss of cholinergic neurons in synapses of the basal forebrain and neuronal death. Exact pathology of the disease is not yet known however, many hypotheses have been proposed for its treatment. The available treatments including monotherapies and combination therapies are not able to combat the disease effectively because of its complex pathological mechanism. A multipotent drug for AD has the potential to bind or inhibit multiple targets responsible for the progression of the disease like aggregated Abeta, hyperphosphorylated tau proteins, cholinergic and adrenergic receptors, MAO enzymes, overactivated N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor etc. The traditional approach of one disease-one target-one drug has been rationalized to one drug-multi targets for the chronic diseases like AD and cancer. Thus, over the last decade research focus has been shifted towards the development of multi target directed ligands (MTDLs) which can simultaneously inhibit multiple targets and stop or slow the progression of the disease. The MTDLs can be more effective against AD and eliminate any possibility of drug-drug interactions. Many important active pharmacophore units have been fused, merged or incorporated into different scaffolds to synthesize new potent drugs. In the current article, we have described various hypothesis for AD and effectiveness of the MTDLs treatment strategy is discussed in detail. Different chemical scaffolds and their synthetic strategies have been described and important functionalities are identified in the chemical scaffold that have the potential to bind to the multiple targets. The important leads identified in this study with MTDL characteristics have the potential to be developed as drug candidates for the effective treatment of AD.
ESTHER : Kumar_2022_Bioorg.Med.Chem_61_116742
PubMedSearch : Kumar_2022_Bioorg.Med.Chem_61_116742
PubMedID: 35398739

Title : Insecticide susceptibility vis--vis molecular variations in geographical populations of fall armyworm, Spodoptera frugiperda (J.E. smith) in India - Kumar_2022_3.Biotech_12_241
Author(s) : Kumar S , Suby SB , Kumar N , Sekhar JC , Nebapure S , Mahapatro GK
Ref : 3 Biotech , 12 :241 , 2022
Abstract : In an emergency response to the introduction, subsequent detection and rapid spread of the invasive insect pest fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) in the country, Government of India offered ad-hoc approval for few pesticide molecules namely, emamectin benzoate, spinetoram, chlorantraniliprole, novaluron, thiodicarb, and lambda-cyhalothrin for FAW management in corn crop across the country. Five major maize (corn) growing geographical areas (i.e., Bihar, Delhi, Karnataka, Punjab and Tamil Nadu) were selected during the main crop season of 2020 (Oct-Nov), and sampled for the target-insect populations. The insect populations were lab-reared on maize leaves (15-20 days old); the F(1) generation insects (third instar, 25-30 mg/larva) were subjected to bioassay to determine susceptibility levels of FAW against ad-hoc recommended insecticides. The previously reported target-site molecular variations in the genes ace, encoding acetylcholinesterase (AChE), and vgsc, encoding voltage-gated sodium channel were analyzed. Among the five test-populations, Bihar test-population recorded least susceptibility to all the test-pesticides, whereas the South Indian populations (Karnataka, Tamil Nadu) were found most susceptible. North Indian and South Indian test-insect populations formed two distinct groups in terms of susceptibility levels, speculatively on account of prevailing climatic factors. Being the population with least ace mutation frequency, but with the higher resistance ratio for all the test-pesticides, Bihar insect population implies a bigger role of broad range detoxification machinery than the narrow scope of target site insensitivity. Though, resistance has not developed to the recommended insecticides by FAW, except the case of low-medium resistance development; which is better explained due to behavioural avoidance of synthetic pyrethroid (lambda-cyhalothrin). However, there is no room for complacency. Resistance-monitoring tools such as location/region-specific determination of discriminating diagnostic concentrations/doses for FAW in recommended insecticides are to be devised at the earliest. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-022-03303-2.
ESTHER : Kumar_2022_3.Biotech_12_241
PubMedSearch : Kumar_2022_3.Biotech_12_241
PubMedID: 36032511

Title : Metal determination and biochemical status of marine fishes facilitate the biomonitoring of marine pollution - Kumar_2021_Mar.Pollut.Bull_170_112682
Author(s) : Kumar N , Bhushan S , Gupta SK , Kumar P , Chandan NK , Singh DK
Ref : Mar Pollut Bull , 170 :112682 , 2021
Abstract : In the present study, the bioaccumulation of chromium, manganese, cobalt, copper, zinc, selenium, arsenic, strontium, cadmium, tin, antimony and lead in tissues of thirty marine fish species collected from New Ferry Whorf, Sassoon dock and Versova fishing harbour in Mumbai, India, were analysed. The bioaccumulation patterns of these twelve elements were determined to assess pollution biomarkers based on cellular and oxidative stresses. Catalase, superoxide dismutase and glutathione-s-transferase, glycolytic enzymes viz. lactate dehydrogenase and malate dehydrogenase, protein metabolism enzymes viz. aspartate transferase and alanine transferase, and lipid peroxidation were significantly higher in muscle and gill tissues. The activities of the neurotransmitter enzyme acetylcholine esterase in muscle and brain tissues was inhibited due to pollution. This study suggested that biochemical attributes such as oxidative stress enzymes, cellular biomarkers, neurotransmitter enzymes and metal and metalloid contamination could be successfully employed, even at low concentrations, as reliable biomarkers for biomonitoring of contaminated marine ecosystems.
ESTHER : Kumar_2021_Mar.Pollut.Bull_170_112682
PubMedSearch : Kumar_2021_Mar.Pollut.Bull_170_112682
PubMedID: 34218033

Title : Design, Synthesis, biological investigations and molecular interactions of triazole linked tacrine glycoconjugates as Acetylcholinesterase inhibitors with reduced hepatotoxicity - Kaur_2021_Bioorg.Chem_118_105479
Author(s) : Kaur Gulati H , Choudhary S , Kumar N , Ahmed A , Bhagat K , Vir Singh J , Singh A , Kumar A , Singh Bedi PM , Singh H , Mukherjee D
Ref : Bioorg Chem , 118 :105479 , 2021
Abstract : Tacrine is a known Acetylcholinesterase (AChE) inhibitors having hepatotoxicity as main liability associated with it. The present study aims to reduce its hepatotoxicity by synthesizing tacrine linked triazole glycoconjugates via Huisgen's [3 + 2] cycloaddition of anomeric azides and terminal acetylenes derived from tacrine. A series of triazole based glycoconjugates containing both acetylated (A-1 to A-7) and free sugar hydroxyl groups (A-8 to A-14) at the amino position of tacrine were synthesized in good yield taking aid from molecular docking studies and evaluated for their in vitro AChE inhibition activity as well as hepatotoxicity. All the hybrids were found to be non-toxic on HePG2 cell line at 200 microM (100 % cell viability) as compared to tacrine (35 % cell viability) after 24 h of incubation period. Enzyme kinetic studies carried out for one of the potent hybrids in the series A-1 (IC(50) 0.4 microM) revealed its mixed inhibition approach. Thus, compound A-1 can be used as principle template to further explore the mechanism of action of different targets involved in Alzheimer's disease (AD) which stands as an adequate chemical probe to be launched in an AD drug discovery program.
ESTHER : Kaur_2021_Bioorg.Chem_118_105479
PubMedSearch : Kaur_2021_Bioorg.Chem_118_105479
PubMedID: 34801945

Title : Further SAR studies on natural template based neuroprotective molecules for the treatment of Alzheimer's disease - Singh_2021_Bioorg.Med.Chem_46_116385
Author(s) : Singh YP , Shankar G , Jahan S , Singh G , Kumar N , Barik A , Upadhyay P , Singh L , Kamble K , Singh GK , Tiwari S , Garg P , Gupta S , Modi G
Ref : Bioorganic & Medicinal Chemistry , 46 :116385 , 2021
Abstract : In our earlier paper, we described ferulic acid (FA) template based novel series of multifunctional cholinesterase (ChE) inhibitors for the management of AD. This report has further extended the structure-activity relationship (SAR) studies of this series of molecules in a calibrated manner to improve upon the ChEs inhibition and antioxidant property to identify the novel potent multifunctional molecules. To investigate the effect of replacement of phenylpiperazine ring with benzylpiperazine, increase in the linker length between FA and substituted phenyl ring, and replacement of indole moiety with tryptamine on this molecular template, three series of novel molecules were developed. All synthesized compounds were tested for their acetyl and butyryl cholinestrases (AChE and BChE) inhibitory properties. Enzyme inhibition and PAS binding studies identified compound 13b as a lead molecule with potent inhibitor property towards AChE/BChE (AChE IC(50) = 0.96 +/- 0.14 microM, BChE IC(50) = 1.23 +/- 0.23 microM) compared to earlier identified lead molecule EJMC-G (AChE IC(50) = 5.74 +/- 0.13 microM, BChE IC(50) = 14.05 +/- 0.10 microM, respectively). Molecular docking and dynamics studies revealed that 13b fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Trp86, Ser125, Glu202, Trp 286, Phe295, Tyr 337 in AChE, and with Trp 82, Gly115, Tyr128, and Ser287 in BChE. The compound, 13b was found to be three times more potent antioxidant in a DPPH assay (IC(50) = 20.25 +/- 0.26 microM) over the earlier identified EJMC-B (IC(50) = 61.98 +/- 0.30 microM) and it also was able to chelate iron. Co-treatment of 13b with H(2)O(2), significantly attenuated and reversed H(2)O(2)-induced toxicity in the SH-SY5Y cells. The parallel artificial membrane permeability assay-blood brain barrier (PAMPA-BBB) revealed that 13b could cross BBB efficiently. Finally, the in-vivo efficacy of 13b at dose of 10 mg/kg in scopolamine AD model has been demonstrated. The present study strongly suggests that the naturally inspired multifunctional molecule 13b may behave as a potential novel therapeutic agent for AD management.
ESTHER : Singh_2021_Bioorg.Med.Chem_46_116385
PubMedSearch : Singh_2021_Bioorg.Med.Chem_46_116385
PubMedID: 34481338

Title : Pharmacokinetic and pharmacodynamic evaluation of nasal liposome and nanoparticle based rivastigmine formulations in acute and chronic models of Alzheimer's disease - Rompicherla_2021_Naunyn.Schmiedebergs.Arch.Pharmacol__
Author(s) : Rompicherla SKL , Arumugam K , Bojja SL , Kumar N , Rao CM
Ref : Naunyn Schmiedebergs Arch Pharmacol , : , 2021
Abstract : With the increasing aging population and progressive nature of the disease, Alzheimer's disease (AD) poses to be an oncoming epidemic with limited therapeutic strategies. It is characterized by memory loss, behavioral instability, impaired cognitive function, predominantly, cognitive inability manifested due to the accumulation of beta-amyloid, with malfunctioned cholinergic system. Rivastigmine, a reversible dual cholinesterase inhibitor, is a more tolerable and widely used choice of drug for AD. However, rivastigmine being hydrophilic and undergoing the first-pass metabolism exhibits low CNS bioavailability. Nanoformulations including liposomes and PLGA nanoparticles can encapsulate hydrophilic drugs and deliver them efficiently to the brain. Besides, the nasal route is receiving considerable attention recently, due to its direct access to the brain. Therefore, the present study attempts to evaluate the pharmacokinetic and pharmacodynamic properties of nasal liposomal and PLGA nanoparticle formulations of rivastigmine in acute scopolamine-induced amnesia and chronic colchicine induced cognitive dysfunction animal models, and validate the best formulation by employing pharmacokinetic and pharmacodynamic (PK-PD) modeling. Nasal liposomal rivastigmine formulation showed the best pharmacokinetic features with rapid onset of action (Tmax = 5 min), higher Cmax (1489.5 +/- 620.71), enhanced systemic bioavailability (F = 118.65 +/- 23.54; AUC = 35,921.75 +/- 9559.46), increased half-life (30.92 +/- 8.38 min), and reduced clearance rate (Kel (1/min) = 0.0224 +/- 0.006) compared to oral rivastigmine (Tmax = 15 min; Cmax = 56.29 +/- 27.05; F = 4.39 +/- 1.82; AUC = 1663.79 +/- 813.54; t1/2 = 13.48 +/- 5.79; Kel (1/min) = 0.0514 +/- 0.023). Further, the liposomal formulation significantly rescued the memory deficit induced by scopolamine as well as colchicine superior to other formulations as assessed in Morris water maze and passive avoidance tasks. PK-PD modeling demonstrated a strong correlation between the pharmacokinetic parameters and acetylcholinesterase inhibition of liposomal formulation.
ESTHER : Rompicherla_2021_Naunyn.Schmiedebergs.Arch.Pharmacol__
PubMedSearch : Rompicherla_2021_Naunyn.Schmiedebergs.Arch.Pharmacol__
PubMedID: 34086100

Title : Transgenerational effects of developmental exposure to chlorpyrifos-oxon in zebrafish (DANIO RERIO) - Schmitt_2020_Toxicol.Appl.Pharmacol_408_115275
Author(s) : Schmitt C , Peterson E , Willis A , Kumar N , McManus M , Subbiah S , Crago J
Ref : Toxicol Appl Pharmacol , 408 :115275 , 2020
Abstract : The organophosphate chlorpyrifos, and its active metabolite chlorpyrifos-oxon (CPO), have been attributed to a number of neurodevelopmental disorders. It is unclear if the adverse effects associated with developmental exposure to the active CPO persist into adulthood and future generations. The goal of this study was to investigate whether CPO-associated changes in embryo-larval zebrafish (ZF) behavior at the F0 5 dpf were manifest throughout the life of the exposed F0, and are inherited by subsequent generations. For this study, embryos were exposed to chlorpyrifos-oxon at the environmentally relevant concentration of 0.01 microg/L and a high concentration of 50 microg/L starting at 4 hpf to 5 dpf, and then raised to F2. There was a significant decrease in distance traveled with 5 dpf F0 ZF exposed to the 50 microg/L CPO, with alterations in noncholinergic genes CFOS and LINGO, and alterations in global DNA methylation. CPO-related behavioral effects were ameliorated by day 21 through the F1 generation. This trend changed with hyperactive behavior, increase acetylcholine concentration in F2 zebrafish that were exposed to 50 microg/L CPO during the F0 development. There was also an increase in AChE activity and hypermethylation in F2 0.01 microg/L exposure larvae, indicating that even low dose exposures can have transgenerational effects. Results from this study demonstrate that early life stage exposures to CPO can lead to epigenetic changes in neurological activity, which may lead to alterations in response to CPO in future generations. ABSTRACT SUMMARY: This study identified a correlation between CPO exposure during F0 development and significant differences in F2 behavioral, AChE activity and neurotransmitter concentration.
ESTHER : Schmitt_2020_Toxicol.Appl.Pharmacol_408_115275
PubMedSearch : Schmitt_2020_Toxicol.Appl.Pharmacol_408_115275
PubMedID: 33049267
Gene_locus related to this paper: danre-ACHE

Title : Anti-snake venom and methanolic extract of Andrographis paniculata: a multipronged strategy to neutralize Naja naja venom acetylcholinesterase and hyaluronidase - Nayak_2020_3.Biotech_10_476
Author(s) : Nayak AG , Kumar N , Shenoy S , Roche M
Ref : 3 Biotech , 10 :476 , 2020
Abstract : The study investigates the ability of methanolic extract of Andrographis paniculata (MAP) to supplement polyvalent anti-snake venom (ASV) in inhibiting neurotoxic enzyme acetylcholinesterase (AChE) and 'spreading factor' hyaluronidase from Naja naja (N.N) venom. AChE and hyaluronidase activity were measured in 100 or 200 microg of crude venom, respectively, and designated as 'control'. In Test Group I, enzyme assays were performed immediately after the addition of ASV/MAP/ASV + MAP to the venom. Inhibition of AChE by ASV (100-367 microg) was 12-17%, and of hyaluronidase (22-660 microg) was 33-41%. Under the same conditions, MAP (100-400 microg) inhibited AChE and hyaluronidase to the extent of 17-33% and 17-52%, respectively. When ASV (220 microg) and MAP (100-200 microg) were added together, AChE and hyaluronidase were inhibited to a greater extent from 39-63 to 36-44%, than when either of them was used alone. In Test Group 2, the venom was incubated with ASV/MAP/ASV + MAP for 10-30 min at 37 degreeC prior to the assay which enhanced AChE inhibition by 6%, 82% and 18% respectively, when compared to Test Group I. Though there was no change in inhibition of hyaluronidase in the presence of ASV, MAP could further increase the extent of inhibition by 27% and ASV + MAP upto 4%. In Test Group III, venom and substrate were incubated for 90 min and hyaluronidase activity was measured after the addition of inhibitors. Here, ASV + MAP caused increased inhibition by 69% compared to ASV alone. The study confirms the ability of phytochemicals in MAP to contribute to a multipronged strategy by supplementing, thereby augmenting the efficacy of ASV.
ESTHER : Nayak_2020_3.Biotech_10_476
PubMedSearch : Nayak_2020_3.Biotech_10_476
PubMedID: 33083200

Title : Drug repurposing for Alzheimer's disease: in silico and in vitro investigation of FDA-approved drugs as acetylcholinesterase inhibitors - Kumar_2020_J.Biomol.Struct.Dyn__1
Author(s) : Kumar N , Gahlawat A , Kumar RN , Singh YP , Modi G , Garg P
Ref : J Biomol Struct Dyn , :1 , 2020
Abstract : Alzheimer's disease (AD) is one of the most familiar multifactorial and complex neurodegenerative disorders characterized by loss of cholinergic neurons in the brain. The various attempts for drug development to treat AD have been hampered by largely unsuccessful clinical trials in the last two decades. Developing a new drug from scratch takes enormous amounts of time, effort and money, mainly due to several barriers in the therapeutic drug development process. Drug repurposing strategy resuscitates this slow drug discovery process by finding new uses and clinical indications for existing drugs. This study is focused on the cholinergic hypothesis, a well-established target of the clinically available drugs in the market for the treatment of AD. The computational virtual screening (VS) led to the identification of thiazolidinedione (TZD, antidiabetic) and aminoquinoline (antimalarial) class of drugs as acetylcholinesterase (AChE) inhibitors. Intriguingly, rosiglitazone (RGZ) and hydroxychloroquine (HCQ) were found to be mild-to-moderate inhibitors of hAChE (human acetylcholinesterase) in our enzyme inhibition studies which are complementary to our computational studies. On the basis of our computational and experimental studies, it can be suggested that the beneficial effect of RGZ and HCQ in AD patients reported in the literature may partly be due to their AChE inhibitory property. The VS also led to the identification of antifungal drugs miconazole and oxiconazole as potential AChE inhibitors. The molecular dynamics (MD) simulation of the potential hits belonging to TZD, aminoquinoline and azoles class were also carried out. The MD simulations studies revealed detailed computational insights related to molecular interactions and protein-ligand stability for selected hits. Communicated by Ramaswamy H. Sarma.
ESTHER : Kumar_2020_J.Biomol.Struct.Dyn__1
PubMedSearch : Kumar_2020_J.Biomol.Struct.Dyn__1
PubMedID: 33170091

Title : New coumarin-benzotriazole based hybrid molecules as inhibitors of acetylcholinesterase and amyloid aggregation - Singh_2020_Bioorg.Med.Chem.Lett_30_127477
Author(s) : Singh A , Sharma S , Arora S , Attri S , Kaur P , Kaur Gulati H , Bhagat K , Kumar N , Singh H , Vir Singh J , Mohinder Singh Bedi P
Ref : Bioorganic & Medicinal Chemistry Lett , 30 :127477 , 2020
Abstract : A novel series of triazole tethered coumarin-benzotriazole hybrids based on donepezil skeleton has been designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Among the synthesized compounds 13b showed most potent acetylcholinesterase (AChE) inhibition (IC(50) = 0.059 microM) with mixed type inhibition scenario. Structure-activity relationship revealed that three-carbon alkyl chain connecting coumarin and triazole is well tolerable for inhibitory potential. Hybrids obtained from 4-hydroxycoumarin and 1-benzotriazole were most potent AChE inhibitors. The inhibitory potential of all compounds against butyrylcholinesterase was also evaluated but all showed negligible activity suggesting that the hybrid molecules are selective AChE inhibitors. 13b (most potent AChE inhibitor) also showed copper-induced Abeta(1-42) aggregation inhibition (34.26% at 50 microM) and chelating properties for metal ions (Cu(2+), Fe(2+,) and Zn(2+)) involved in AD pathogenesis along with DNA protective potential against degenerative actions of OH radicals. Molecular modelling studies confirm the potential of 13b in blocking both PAS and CAS of AChE. In addition, interactions of 13b with Abeta(1-42) monomer are also streamlined. Therefore, hybrid 13b can act as an effective hit lead molecule for further development of selective AChE inhibitors as multifunctional anti-Alzheimer's agents.
ESTHER : Singh_2020_Bioorg.Med.Chem.Lett_30_127477
PubMedSearch : Singh_2020_Bioorg.Med.Chem.Lett_30_127477
PubMedID: 32781220

Title : A Broad Temperature Active Lipase Purified From a Psychrotrophic Bacterium of Sikkim Himalaya With Potential Application in Detergent Formulation - Kumar_2020_Front.Bioeng.Biotechnol_8_642
Author(s) : Kumar A , Mukhia S , Kumar N , Acharya V , Kumar S , Kumar R
Ref : Front Bioeng Biotechnol , 8 :642 , 2020
Abstract : Bacterial lipases with activity spanning over a broad temperature and substrate range have several industrial applications. An efficient enzyme-producing bacterium Chryseobacterium polytrichastri ERMR1:04, previously reported from Sikkim Himalaya, was explored for purification and characterization of cold-adapted lipase. Optimum lipase production was observed in 1% (v/v) rice bran oil, pH 7 at 20degC. Size exclusion and hydrophobic interaction chromatography purified the enzyme up to 21.3-fold predicting it to be a hexameric protein of 250 kDa, with 39.8 kDa monomeric unit. MALDI-TOF-MS analysis of the purified lipase showed maximum similarity with alpha/beta hydrolase (lipase superfamily). Biochemical characterization of the purified enzyme revealed optimum pH (8.0), temperature (37degC) and activity over a temperature range of 5-65degC. The tested metals (except Cu(2+) and Fe(2+)) enhanced the enzyme activity and it was tolerant to 5% (v/v) methanol and isopropanol. The Km and Vmax values were determined as 0.104 mM and 3.58 U/mg, respectively for p-nitrophenyl palmitate. Bioinformatics analysis also supported in vitro findings by predicting enzyme's broad temperature and substrate specificity. The compatibility of the purified lipase with regular commercial detergents, coupled with its versatile temperature and substrate range, renders the given enzyme a promising biocatalyst for potential detergent formulations.
ESTHER : Kumar_2020_Front.Bioeng.Biotechnol_8_642
PubMedSearch : Kumar_2020_Front.Bioeng.Biotechnol_8_642
PubMedID: 32671041

Title : Candida antarctica lipase-B-catalyzed kinetic resolution of 1,3-dialkyl-3-hydroxymethyl oxindoles - Kumar_2020_Chirality_32_1377
Author(s) : Kumar N , Kumar A , Sahoo SC , Chimni SS
Ref : Chirality , 32 :1377 , 2020
Abstract : Candida antarctica (CAL-B) lipase-catalyzed resolution of 1,3-dialkyl-3-hydroxymethyl oxindoles has been performed to obtain (R)-1,3-dialkyl-3-acetoxymethyl oxindoles with up to 99% ee and (S)-1,3-dialkyl-3-hydroxymethyl oxindoles with up to 78% ee using vinyl acetate as acylating agent and acetonitrile as solvent transforming (S)-3-allyl-3-hydroxymethyl oxindole to (3S)-1'-benzyl-5-(iodomethyl)-4,5-dihydro-2H-spiro[furan-3,3'-indolin]-2'-one. The optically active 3-substituted-3-hydroxymethyl oxindoles and spiro-oxindoles are among the key synthons in the synthesis of potentially biologically active molecules.
ESTHER : Kumar_2020_Chirality_32_1377
PubMedSearch : Kumar_2020_Chirality_32_1377
PubMedID: 33141985

Title : Comparative analyses of the neurobehavioral, molecular, and enzymatic effects of organophosphates on embryo-larval zebrafish (Danio rerio) - Schmitt_2019_Neurotoxicol.Teratol_73_67
Author(s) : Schmitt C , McManus M , Kumar N , Awoyemi O , Crago J
Ref : Neurotoxicology & Teratology , 73 :67 , 2019
Abstract : Organophosphates insecticides (OPs) are common surface water contaminants in both urban and agricultural landscapes. Neurobehavioral effects on larval fish are known to occur at concentrations higher than those reported in the environment. The aim of this study was to perform a comparative analysis of neurobehavioral, molecular, and biochemical responses of four OPs (diazinon, dichlorvos, malathion, methyl-parathion) via the following endpoint measurements: distance traveled, velocity, gene expression (AChE, c-Fos, LINGO-1B, GRIN-1B), enzymatic acetylcholinesterase (AChE) activity, and carboxylesterase (CES) activity. OP exposures (5 hpf - 120 dpf) on embryo-larval zebrafish (Danio rerio) were assessed using a larval zebrafish behavior assay at concentrations: 0.01, 0.1, 10, and 100mug/L. Individual OPs had varying degrees of neurotoxicity. Significant hypoactivity was observed in the 100mug/L treatments for diazinon and malathion (p<0.05) as compared to the controls. Diazinon-exposed larvae exhibited a 26% locomotor decrease, and hypoactivity was observed in malathion-exposed larvae at a reduction of 22% and 29% for distance traveled and velocity, respectively. Gene regulation and enzymatic activity changes were measured for both 0.1 and 100mug/L exposures across OP treatments. Increased CES activity was observed for the 0.1mug/L treatments of diazinon and methyl-parathion as well as the 100mug/L treatment of dichlorvos; meanwhile, decreased CES activity was observed for 100mug/L treatments of diazinon and malathion. Relative enzymatic activity of AChE was inhibited as compared to the control for the 0.1mug/L diazinon. No other treatment group exhibited a significant effect on biochemical AChE activity; however, AChE upregulation was observed in the 0.1mug/L exposure for diazinon, dichlorvos, and malathion. Methyl-parathion was observed to downregulate c-Fos at 0.1mug/L exposure. Malathion upregulated LINGO-1B at 100mug/L, a gene associated with neuronal regeneration; meanwhile, downregulation of LINGO-1B was observed for 0.1mug/L exposure of methyl-parathion. Additional downregulation was observed for GRIN-1B in the 100mug/L diazinon, 100mug/L dichlorvos, and 0.1mug/L methyl-parathion treatments. Exposure of ZF embryos to independent concentrations of 100mug/L concentrations of diazinon and malathion resulted in hypoactivity and decreased CES activity at 5 dfp. No changes in swimming behavior were observed for either the 0.1mug/L or 100mug/L dichlorvos or methyl-parathion treatments. Observations from this study indicate that AChE inhibition may not be the most sensitive biomarker of OP pesticide exposure in zebrafish. Rather, the enzyme CES demonstrated higher sensitivity as a biomarker of OP toxicity.
ESTHER : Schmitt_2019_Neurotoxicol.Teratol_73_67
PubMedSearch : Schmitt_2019_Neurotoxicol.Teratol_73_67
PubMedID: 30978384

Title : Bioresolution of racemic phenyl glycidyl ether by a putative recombinant epoxide hydrolase from Streptomyces griseus NBRC 13350 - Saini_2017_World.J.Microbiol.Biotechnol_33_82
Author(s) : Saini P , Kumar N , Wani SI , Sharma S , Chimni SS , Sareen D
Ref : World J Microbiol Biotechnol , 33 :82 , 2017
Abstract : In order to produce enantiomerically pure epoxides for the synthesis of value-added chemicals, a novel putative epoxide hydrolase (EH) sgeh was cloned and overexpressed in pET28a/Escherichia coli BL21(DE3). The 1047 bp sgeh gene was mined from Streptomyces griseus NBRC 13350 genome sequence. The recombinant hexahistidyl-tagged SGEH was purified (16.6-fold) by immobilized metal-affinity chromatography, with 90% yield as a homodimer of 100 kDa. The recombinant E. coli whole cells overexpressing SGEH could kinetically resolve racemic phenyl glycidyl ether (PGE) into (R)-PGE with 98% ee, 40% yield, and enantiomeric ratio (E) of 20. This was achieved under the optimized reaction conditions i.e. cell/substrate ratio of 20:1 (w/w) at pH 7.5 and 20 degrees C in 10% (v/v) dimethylformamide (DMF) in a 10 h reaction. 99% enantiopure (R)-PGE was obtained when the reaction time was prolonged to 12 h with a yield of 34%. In conclusion, an economically viable and environment friendly green process for the production of enantiopure (R)-PGE was developed by using wet cells of E. coli expressing recombinant SGEH.
ESTHER : Saini_2017_World.J.Microbiol.Biotechnol_33_82
PubMedSearch : Saini_2017_World.J.Microbiol.Biotechnol_33_82
PubMedID: 28378221
Gene_locus related to this paper: strgg-b1vn62

Title : Effect of insulin on spatial memory in aluminum chloride-induced dementia in rats - Nampoothiri_2017_Neuroreport_28_540
Author(s) : Nampoothiri M , Kumar N , Venkata Ramalingayya G , Gopalan Kutty N , Krishnadas N , Mallikarjuna Rao C
Ref : Neuroreport , 28 :540 , 2017
Abstract : Latest reports suggest the involvement of insulin in modulating memory. A few published in-vitro studies favor the antidementia effect of insulin. Thus, the present study aimed to evaluate the prophylactic role of insulin and its combination with glucose and its possible mechanism(s) in an aluminum chloride (AlCl3)-induced cognitive dysfunction model in rodents, with a special focus on memory centers namely, the hippocampus and the frontal cortex. Male Wistar rats were exposed to AlCl3 (175 mg/kg orally) for 60 days. Insulin (0.5 IU/kg), Insulin (0.5 IU/kg) in combination with glucose (200 mg/kg), and rivastigmine (1 mg/kg) were administered intraperitoneally 45 min before the administration of AlCl3 for 60 days. Spatial memory was assessed using the Morris water-maze test. After 60 days of treatment, animals were killed, and the hippocampus and frontal cortex were collected and analyzed for acetylcholinesterase activity and antioxidant enzyme level. Blood glucose levels were also analyzed. Treatment with the standard drug, rivastigmine (1 mg/kg), produced a significant reduction in escape latency and increased the time spent in the target quadrant compared with the AlCl3-treated group. Insulin and its combination with glucose could not inhibit the behavioral impairments in aluminum-exposed rats. Treatment with insulin alone and its combination with glucose reversed the increased glucose levels. Insulin alone and its combination with glucose could not inhibit aluminum-induced oxidative stress and impaired cholinergic transmission in the hippocampus and frontal cortex regions. The study suggests the inability of prophylactic insulin administration against cognitive dysfunction induced by environmental toxin (AlCl3) in the hippocampus and the frontal cortex.
ESTHER : Nampoothiri_2017_Neuroreport_28_540
PubMedSearch : Nampoothiri_2017_Neuroreport_28_540
PubMedID: 28498150

Title : Modulatory Role of Simvastatin against Aluminium Chloride-Induced Behavioural and Biochemical Changes in Rats - Nampoothiri_2015_Behav.Neurol_2015_210169
Author(s) : Nampoothiri M , John J , Kumar N , Mudgal J , Nampurath GK , Chamallamudi MR
Ref : Behav Neurol , 2015 :210169 , 2015
Abstract : Objectives. Aluminium, a neurotoxic agent in humans, has been implicated in the pathogenesis of neurodegenerative disorders. In this study, we examined the behavioral and biochemical effects of aluminium in rats with special emphasis on memory centres, namely, hippocampus and frontal cortex. Further, the effect of simvastatin treatment on aluminium intoxication was evaluated. Methods. Rats were exposed to aluminium chloride (AlCl3) for 60 days. Simvastatin (10 mg/kg/p.o.) and rivastigmine (1 mg/kg/p.o.) were administered daily prior to AlCl3. Behavioral parameters were assessed using Morris water maze test and actophotometer followed by biochemical investigations, namely, acetylcholinesterase (AChE) activity, TNF-alpha level, antioxidant enzymes (GSH, catalase), lipid peroxidation, and nitrite level in hippocampus and frontal cortex. Triglycerides, total cholesterol, LDL, and HDL levels in serum were also determined. Key Findings. Simvastatin treatment improved cognitive function and locomotor activity in rats. Simvastatin reversed hyperlipidemia and significantly rectified the deleterious effect of AlCl3 on AChE activity. Further, in hippocampus and frontal cortex, aluminium-induced elevation in nitrite and TNF-alpha and reduction in antioxidant enzymes were inhibited by simvastatin. Conclusion. To conclude, the present study suggests that simvastatin per se protects the neurons in hippocampus and frontal cortex from AlCl3, an environmental toxin.
ESTHER : Nampoothiri_2015_Behav.Neurol_2015_210169
PubMedSearch : Nampoothiri_2015_Behav.Neurol_2015_210169
PubMedID: 25802481

Title : Sesamol, a lipid lowering agent, ameliorates aluminium chloride induced behavioral and biochemical alterations in rats - John_2015_Pharmacogn.Mag_11_327
Author(s) : John J , Nampoothiri M , Kumar N , Mudgal J , Nampurath GK , Chamallamudi MR
Ref : Pharmacogn Mag , 11 :327 , 2015
Abstract : BACKGROUND: Sesame oil from the seeds of Sesamum indicum Linn. (Pedaliaceae) has been used traditionally in Indian medical practice of Ayurveda in the treatment of central nervous system disorders and insomnia. A few published reports favor the anti-dementia effect of sesamol (SML), an active constituent of sesame oil. OBJECTIVE: Thus, the present study was aimed to explore the anti-dementia effect and possible mechanism (s) of SML in aluminium chloride (AlCl3)-induced cognitive dysfunction model in rodents with special emphasis on memory centers viz., hippocampus and frontal cortex.
METHODS: Male Wistar rats were exposed to AlCl3 (175 mg/kg p.o.) for 60 days. SML (10 and 20 mg/kg) and rivastigmine (1 mg/kg) were administered orally 45 min before administration of AlCl3 for 60 days. Spatial memory was assessed using Morris water maze test. After 60 days of treatment animals were sacrificed, hippocampus and frontal cortex were collected and analyzed for acetylcholinesterase (AChE) activity, tumor necrosis factor (TNF-alpha) level, antioxidant enzymes (Glutathione, catalase), lipid peroxidation, and nitrite level. The circulating triglycerides, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels were also analyzed.
RESULTS: SML significantly prevented behavioral impairments in aluminium-exposed rats. Treatment with SML reversed the increased cholesterol, triglycerides and LDL while raised the HDL levels. SML significantly corrected the effect of AlCl3 on AChE activity. Further, SML reversed the elevated nitric oxide, TNF-alpha and reduced antioxidant enzymes in hippocampus and frontal cortex. CONCLUSION: The present study suggests the neuro-protection by SML against cognitive dysfunction induced by environmental toxin (AlCl3) in hippocampus and frontal cortex.
ESTHER : John_2015_Pharmacogn.Mag_11_327
PubMedSearch : John_2015_Pharmacogn.Mag_11_327
PubMedID: 25829772

Title : Lipotropes promote immunobiochemical plasticity and protect fish against low-dose pesticide-induced oxidative stress - Muthappa_2014_Cell.Stress.Chaperones_19_61
Author(s) : Muthappa NA , Gupta S , Yengkokpam S , Debnath D , Kumar N , Pal AK , Jadhao SB
Ref : Cell Stress Chaperones , 19 :61 , 2014
Abstract : An experiment was conducted to evaluate the role of different lipotropes in modulating immunity and biochemical plasticity under conditions of sublethal low-dose pesticide-induced stress in fish. Labeo rohita fish fingerlings were divided in two sets with one set of fish continuously exposed to low-dose endosulfan (1/10th of 96-h LC50) for 21 days, the other was unexposed, and both sets of fish were fed with practical diets supplemented with either 2 % lecithin, 0.5 % betaine, or 0.1 % choline and compared against unsupplemented diet. Low-dose endosulfan exposure had adverse effects (P < 0.05/P < 0.01) on hematological profile (erythrocyte count, hemoglobin, and hematocrit), serum protein (total protein, albumin, and globulin) and lipid profile (cholesterol and triglyceride), anti-oxidative status (ascorbic acid content of muscle, liver, brain, and kidney and activity of anti-oxidative enzymes: catalase and superoxide dismutase), neurotransmission (acetylcholinesterase activity in muscle and brain), immunological attributes (WBC count, albumin to globulin ratio, phagocytic activity, and serum cortisol), and metabolic plasticity as revealed from enzyme activities (muscle lactate dehydrogenase, liver and kidney glucose-6-phosphatase dehydrogenase-G6PDH activity). Dietary lipotropes prevented these effects completely or partially and the effects were lipotrope dependent. Kinetics (maximum velocity value V max, catalytic efficiency and Michaelis constant K m) of G6PDH enzyme from crude extracts of liver and kidney indicated inhibition due to endosulfan but lipotropes could protect enzyme and showed a stabilizing effect. The supplements also helped maintain integrity of histoarchitecture of the hepatocytes in endosulfan-exposed fish to a great extent. Feeding lipotropes to fish reared in endosulfan-free water also improved hematological and serum protein and lipid profiles and were immunostimulatory. In conclusion, dietary lipotropes, especially betaine and lecithin at the levels used, improve erythropoiesis, serum protein and lipid profile, anti-oxidant status, immunocompetence, neurotransmission, and protect the livers of L. rohita fingerlings even when continuously exposed to low-dose endosulfan.
ESTHER : Muthappa_2014_Cell.Stress.Chaperones_19_61
PubMedSearch : Muthappa_2014_Cell.Stress.Chaperones_19_61
PubMedID: 23666764

Title : Genome Sequence of the Indian Bison Type Biotype of Mycobacterium avium subsp. paratuberculosis Strain S5 - Singh_2013_Genome.Announc_1_e00005
Author(s) : Singh SV , Kumar N , Singh SN , Bhattacharya T , Sohal JS , Singh PK , Singh AV , Singh B , Chaubey KK , Gupta S , Sharma N , Kumar S , Raghava GP
Ref : Genome Announc , 1 : , 2013
Abstract : We report the 4.79-Mb genome sequence of the "Indian Bison Type" biotype of Mycobacterium avium subsp. paratuberculosis strain S5, isolated from a terminally sick Jamunapari goat at the CIRG (Central Institute for Research on Goats) farm in India. This draft genome will help in studying novelties of this biotype, which is widely distributed in animals and human beings in India.
ESTHER : Singh_2013_Genome.Announc_1_e00005
PubMedSearch : Singh_2013_Genome.Announc_1_e00005
PubMedID: 23469332
Gene_locus related to this paper: mycav-DHMA , mycav-Q73T09 , mycpa-MAP2689c

Title : Impact of caffeic acid on aluminium chloride-induced dementia in rats - Khan_2013_J.Pharm.Pharmacol_65_1745
Author(s) : Khan KA , Kumar N , Nayak PG , Nampoothiri M , Shenoy RR , Krishnadas N , Rao CM , Mudgal J
Ref : J Pharm Pharmacol , 65 :1745 , 2013
Abstract : OBJECTIVE: Literature favours the in vitro neuroprotective role of caffeic acid, a naturally derived polyphenolic compound. This study was aimed to investigate the role of caffeic acid in experimental model of Alzheimer's disease.
METHODS: Firstly, caffeic acid was tested for in vitro anticholinesterase potential using rat brain homogenate. Later, in vivo antidementia activity of caffeic acid was assessed against aluminium chloride (AlCl3 )-induced dementia in rats. Behavioural (Morris water maze test) and brain biochemical parameters (acetylcholinesterase (AChE), catalase, glutathione-S-transferase (GST) activity, glutathione (GSH) and nitrite levels) were assessed to correlate the cognitive function with cholinergic transmission and oxidative stress. KEY FINDINGS: Rats administered with caffeic acid showed improved cognitive function in Morris water maze test. The antidementia activity of caffeic acid was confirmed by the reduction in brain AChE activity and nitrite levels. Further, caffeic acid corrected the diminished level of antioxidant enzymes such as catalase, GSH and GST in brain. CONCLUSION: These findings suggest the antidementia activity of caffeic acid against AlCl3 -induced dementia in rats. The outcome of present study offers a wider scope to screen caffeic acid against neurodegeneration associated disorders.
ESTHER : Khan_2013_J.Pharm.Pharmacol_65_1745
PubMedSearch : Khan_2013_J.Pharm.Pharmacol_65_1745
PubMedID: 24236984

Title : Draft Genome Sequence of Plant Growth-Promoting Rhizobacterium Pantoea sp. Strain AS-PWVM4 - Khatri_2013_Genome.Announc_1_e00947
Author(s) : Khatri I , Kaur S , Devi U , Kumar N , Sharma D , Subramanian S , Saini AK
Ref : Genome Announc , 1 : , 2013
Abstract : Nonpathogenic Pantoea spp. have been shown to confer biofertilizer and biocontrol activities, indicating their potential for increasing crop yield. Herein, we provide the high-quality genome sequence of Pantoea sp. strain AS-PWVM4, a Gram-negative motile plant growth-promoting rhizobacterium isolated from a pomegranate plant. The 4.9-Mb genome contains genes related to plant growth promotion and the synthesis of siderophores.
ESTHER : Khatri_2013_Genome.Announc_1_e00947
PubMedSearch : Khatri_2013_Genome.Announc_1_e00947
PubMedID: 24309733
Gene_locus related to this paper: 9entr-u2ml62 , 9entr-u2ml82 , pansa-e6w851

Title : Draft Genome Sequence of a Plant Growth-Promoting Rhizobacterium, Serratia fonticola Strain AU-P3(3) - Devi_2013_Genome.Announc_1_e00946
Author(s) : Devi U , Khatri I , Kumar N , Kumar L , Sharma D , Subramanian S , Saini AK
Ref : Genome Announc , 1 :e00946 , 2013
Abstract : Plant growth-promoting rhizobacteria (PGPR), found in the rhizospheric region of plants, not only suppress plant disease, but also directly improve plant health by improving the availability of nutrients and by providing phytostimulants. Herein, we report the high-quality genome sequence of Serratia fonticola strain AU-P3(3), a PGPR of the pea plant, which confers phosphate solubilization, indole-3-acetic acid production, ammonia production, hydrogen cyanide (HCN) production, and siderophore production and also confers activity against Rhizoctonia species. The 5.02-Mb genome sequence contains genes related to plant growth promotion and biocontrol activities.
ESTHER : Devi_2013_Genome.Announc_1_e00946
PubMedSearch : Devi_2013_Genome.Announc_1_e00946
PubMedID: 24233592
Gene_locus related to this paper: serfo-u2m865 , serpl-s4yi15

Title : Draft Genome Sequence of Plant-Growth-Promoting Rhizobacterium Serratia fonticola Strain AU-AP2C, Isolated from the Pea Rhizosphere - Devi_2013_Genome.Announc_1_e01022
Author(s) : Devi U , Khatri I , Kumar N , Sharma D , Subramanian S , Saini AK
Ref : Genome Announc , 1 : , 2013
Abstract : Plant health can be augmented by plant-growth-promoting rhizobacteria (PGPR) that confer biofertilizer, phytostimulation, and biocontrol activities. Herein, we provide the high-quality draft genome sequence of Serratia fonticola strain AU-AP2C, a Gram-negative motile PGPR of the pea plant, conferring phosphate solubilization, ammonia production, and antifungal activity against Fusarium sp. The 4.9-Mb genome contains genes related to plant growth promotion and synthesis of siderophores.
ESTHER : Devi_2013_Genome.Announc_1_e01022
PubMedSearch : Devi_2013_Genome.Announc_1_e01022
PubMedID: 24309742
Gene_locus related to this paper: serfo-u2m4p0 , serfo-u2m865 , serpl-s4yi15

Title : Anti-oxidative and immuno-hematological status of Tilapia (Oreochromis mossambicus) during acute toxicity test of endosulfan - Kumar_2011_Pestic.Biochem.Physiol_99_45
Author(s) : Kumar N , Antony Jesu Prabhu P , Pal AK , Remya S , Aklakur M , Rana RS , Gupta S , Raman RP , Jadhao SB
Ref : Pesticide Biochemistry and Physiology , 99 :45 , 2011
Abstract : Endosulfan is an organochlorine pesticide widely used in agriculture and hence finds its way into natural water bodies, thus affecting aquatic life. The purpose of this study was to determine LC50 of endosulfan (99%; alpha:beta ratio of 7:3) in Tilapia, Oreochromis mossambicus and study its effect on anti-oxidative enzymes (superoxide dismutase, glutathione-S-transferase and catalase), immuno-hematological profile (RBC, WBC, Hb, serum protein, albumin-A, globulin-G, A/G ratio, phygocytic activity as indicated by nitroblue tetrazolium reduction, serum cortisol and serum lipid peroxidation) and neurotransmitter acetylcholine esterase enzyme activity. The LC50 value at 96 h and 95% confidence limit for tilapia (46.78 g) was estimated as 3.6 ug/L. Activities of anti-oxidative enzymes, immuno-hematological profile, blood glucose and neurotransmitter activity was significantly influenced (P < 0.01) in dose dependent manner. This was reflected in the behavior of fish that was altered from normal during acute toxicity.
ESTHER : Kumar_2011_Pestic.Biochem.Physiol_99_45
PubMedSearch : Kumar_2011_Pestic.Biochem.Physiol_99_45

Title : Factors predicting surgical outcome of thymectomy in myasthenia gravis: A 16-year experience - Kumar_2011_Ann.Indian.Acad.Neurol_14_267
Author(s) : Kumar N , Verma AK , Mishra A , Agrawal G , Agrawal A , Misra UK , Mishra SK
Ref : Ann Indian Acad Neurol , 14 :267 , 2011
Abstract : AIM: To assess the surgical outcome of myasthenia gravis (MG) following thymectomy and to determine the outcome predictors to such therapeutic approach. MATERIALS AND METHODS: This study is a retrospective review of 80 consecutive thymectomies performed for MG over a 16-year period. RESULTS: There were 41 females and 39 males (mean age, 34.32 years) with mean disease duration of 17.45 months prior to surgery. Stagewise distribution of the patients revealed 2.5% in stage I, 48.7% in stage IIA, 33.8% in stage IIB, 8.7% in stage III, and 6.3% in stage IV. The surgical approach was either trans-sternal (n=67) or video-assisted thoracoscopic route (n=13). Follow-up was obtained in 91.2% (n=73) of patients with mean duration of 67.7 months. At their last follow-up, 26.0% were in complete remission, 35.6% were asymptomatic on decreased medications, and 17.8% had clinical improvement on decreased medications. Overall, 79.4% of patients benefited from surgery, 8.2% had unchanged disease status, and 12.3% worsened clinically. Factors influencing favorable outcome include sex, disease stage, gland weight, and preoperative medication with anti-cholinesterase (P<0.05). There was one death in the perioperative period due to septicemia. Two patients died at fourth and seventh month following thymectomy. CONCLUSION: Thymectomy for MG is safe and effective. Certain influencing factors may shape treatment decisions and target higher risk patients.
ESTHER : Kumar_2011_Ann.Indian.Acad.Neurol_14_267
PubMedSearch : Kumar_2011_Ann.Indian.Acad.Neurol_14_267
PubMedID: 22346015

Title : Genomes of two chronological isolates (Helicobacter pylori 2017 and 2018) of the West African Helicobacter pylori strain 908 obtained from a single patient - Avasthi_2011_J.Bacteriol_193_3385
Author(s) : Avasthi TS , Devi SH , Taylor TD , Kumar N , Baddam R , Kondo S , Suzuki Y , Lamouliatte H , Megraud F , Ahmed N
Ref : Journal of Bacteriology , 193 :3385 , 2011
Abstract : The diverse clinical outcomes of colonization by Helicobacter pylori reflect the need to understand the genomic rearrangements enabling the bacterium to adapt to host niches and exhibit varied colonization/virulence potential. We describe the genome sequences of the two serial isolates, H. pylori 2017 and 2018 (the chronological subclones of H. pylori 908), cultured in 2003 from the antrum and corpus, respectively, of an African patient who suffered from recrudescent duodenal ulcer disease. When compared with the genome of the parent strain, 908 (isolated from the antrum of the same patient in 1994), the genome sequences revealed genomic alterations relevant to virulence optimization or host-specific adaptation.
ESTHER : Avasthi_2011_J.Bacteriol_193_3385
PubMedSearch : Avasthi_2011_J.Bacteriol_193_3385
PubMedID: 21515762

Title : Complete genome sequences of rat and mouse segmented filamentous bacteria, a potent inducer of th17 cell differentiation - Prakash_2011_Cell.Host.Microbe_10_273
Author(s) : Prakash T , Oshima K , Morita H , Fukuda S , Imaoka A , Kumar N , Sharma VK , Kim SW , Takahashi M , Saitou N , Taylor TD , Ohno H , Umesaki Y , Hattori M
Ref : Cell Host Microbe , 10 :273 , 2011
Abstract : Segmented filamentous bacteria (SFB) are noncultivable commensals inhabiting the gut of various vertebrate species and have been shown to induce Th17 cells in mice. We present the complete genome sequences of both rat and mouse SFB isolated from SFB-monocolonized hosts. The rat and mouse SFB genomes each harbor a single circular chromosome of 1.52 and 1.59 Mb encoding 1346 and 1420 protein-coding genes, respectively. The overall nucleotide identity between the two genomes is 86%, and the substitution rate was estimated to be similar to that of the free-living E. coli. SFB genomes encode typical genes for anaerobic fermentation and spore and flagella formation, but lack most of the amino acid biosynthesis enzymes, reminiscent of pathogenic Clostridia, exhibiting large dependency on the host. However, SFB lack most of the clostridial virulence-related genes. Comparative analysis with clostridial genomes suggested possible mechanisms for host responses and specific adaptations in the intestine.
ESTHER : Prakash_2011_Cell.Host.Microbe_10_273
PubMedSearch : Prakash_2011_Cell.Host.Microbe_10_273
PubMedID: 21925114
Gene_locus related to this paper: 9clot-g2ifk0

Title : Genome of multidrug-resistant uropathogenic Escherichia coli strain NA114 from India - Avasthi_2011_J.Bacteriol_193_4272
Author(s) : Avasthi TS , Kumar N , Baddam R , Hussain A , Nandanwar N , Jadhav S , Ahmed N
Ref : Journal of Bacteriology , 193 :4272 , 2011
Abstract : Uropathogenic Escherichia coli (UPEC) causes serious infections in people at risk and has a significant environmental prevalence due to contamination by human and animal excreta. In developing countries, UPEC assumes importance in certain dwellings because of poor community/personal hygiene and exposure to contaminated water or soil. We report the complete genome sequence of E. coli strain NA114 from India, a UPEC strain with a multidrug resistance phenotype and the capacity to produce extended-spectrum beta-lactamase. The genome sequence and comparative genomics emanating from it will be significant in under-standing the genetic makeup of diverse UPEC strains and in boosting the development of new diagnostics/vaccines.
ESTHER : Avasthi_2011_J.Bacteriol_193_4272
PubMedSearch : Avasthi_2011_J.Bacteriol_193_4272
PubMedID: 21685291
Gene_locus related to this paper: ecoli-yaim , ecoli-ybff , ecoli-ycfp , ecoli-YFBB , ecoli-yiel , ecoli-yqia , ecoli-YfhR , ecolx-f4suw9 , ecolx-g0dan0

Title : Evaluation of cholinesterase level in an endemic population exposed to malathion suspension formulation as a vector control measure - Lal_2004_Mem.Inst.Oswaldo.Cruz_99_219
Author(s) : Lal CS , Kumar V , Ranjan A , Das VN , Kumar N , Kishore K , Bhattacharya SK
Ref : Mem Inst Oswaldo Cruz , 99 :219 , 2004
Abstract : The manuscript describes a study on the blood cholinesterase (ChE) level in an exposed population at different interval of time after spraying with malathion suspension (SRES) use for kala-azar vector control in an endemic area of Bihar, India. The toxicity of a 5% malathion formulation in the form of a slow release emulsified suspension (SRES) was assessed by measuring serum ChE levels in spraymen and in the exposed population. The study showed a significant decrease in ChE levels in the spraymen (p < 0.01) after one week of spraying and in exposed population one week and one month after of spraying (p < 0.01), but was still within the normal range of ChE concentration, one year after spraying, the ChE concentration in the exposed population was the same as prior to spraying (p > 0.01). On no occasion was the decrease in ChE level alarming. A parallel examination of the clinical status also showed the absence of any over toxicity or any behavioural changes in the exposed population. Hence, it may be concluded that 5% malathion slow release formulation, SRES, is a safe insecticide for use as a vector control measure in endemic areas of kala-azar in Bihar, India so long as good personal protection for spraymen is provided to minimize absorption and it can substitute the presently used traditional DDT spray.
ESTHER : Lal_2004_Mem.Inst.Oswaldo.Cruz_99_219
PubMedSearch : Lal_2004_Mem.Inst.Oswaldo.Cruz_99_219
PubMedID: 15250479

Title : Neostigmine but not edrophonium prolongs the action of mivacurium - Symington_1996_Can.J.Anaesth_43_1220
Author(s) : Symington MJ , Mirakhur RK , Kumar N
Ref : Canadian Journal of Anaesthesia , 43 :1220 , 1996
Abstract : PURPOSE To examine the influence of anticholinesterase drugs neostigmine and edrophonium (which have different effects on plasma cholinesterase activity) administered for antagonism of neuromuscular block on the duration of action of mivacurium (a neuromuscular blocking drug metabolised by plasma cholinesterase). METHODS: This was a randomized study where mivacurium 0.15 mg.kg-1 was administered to a control group or after administration of neostigmine 40 micrograms.kg-1 or edrophonium 1 mg.kg-1 (n = 10 for each group) administered 10 min earlier for antagonism of atracurium-induced neuromuscular block. Neuromuscular block was measured by stimulation of the ulnar nerve in a train-of-four mode (TOF) and measuring the force of contraction of the adductor pollicis muscle. Baseline plasma cholinesterase activity was estimated before drug administration in all the groups and following anticholinesterase administration. RESULTS: The times to recovery of T1 (first response in the TOF) to 25 and 90% of control and of the TOF ratio to 0.7 after 0.15 mg.kg-1 of mivacurium were 47, 65 and 70 min in the neostigmine group; 25, 36 and 36 min in the edrophonium group and 17, 29 and 27 min respectively in the control group (P < 0.01). The plasma cholinesterase activity (PCHE) after neostigmine decreased from 6596 to 1959 U.L-1 (P < 0.001) but there was no change after edrophonium (6140 to 6396 U.L-1).
CONCLUSIONS: The duration of action of mivacurium is prolonged by previous administration of neostigmine and this is most likely to be due to inhibition of PCHE activity.
ESTHER : Symington_1996_Can.J.Anaesth_43_1220
PubMedSearch : Symington_1996_Can.J.Anaesth_43_1220
PubMedID: 8955970

Title : Effects of three reputed carboxylesterase inhibitors upon rat serum esterase activity - Chambers_1991_Neurosci.Biobehav.Rev_15_85
Author(s) : Chambers JP , Hartgraves SL , Murphy MR , Wayner MJ , Kumar N , Valdes JJ
Ref : Neurosci Biobehav Rev , 15 :85 , 1991
Abstract : Rats have very high endogenous levels of serum carboxylesterase (CAE) compared to primates. This difference accounts for the lower sensitivity of rats to toxic organophosphates, which interact with CAE instead of the more critical acetylcholinesterase. Pretreatment of rats with CAE inhibitors potentiates the effects of organophosphates. In this study, the effects of three putative CAE inhibitors, 2-(o-Cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP), bis-p-nitrophenyl-phosphate (BNPP), and tetraisopropyl pyrophosphoramide (Iso-OMPA), on the hydrolysis of several commercially available substrates were determined. Respective kinetic constants Km and Vmax were derived and effects of inhibitors compared using saturating amounts of substrate. Data presented here indicate significant differences in substrate affinity (Km), reactivity (Vmax), as well as effects of inhibitors. CBDP inhibits hydrolysis of specific naphthyl and paranitrophenyl esters at relatively low concentrations (1-10 microM). In contrast, significantly higher concentrations (mM) of BNPP and Iso-OMPA were required for inhibition of serum esterase activity. Of the inhibitors tested, Iso-OMPA in general exhibited the smallest inhibitory effect on ester hydrolysis. Although inhibition of hydrolysis of specific paranitrophenyl and naphthyl esters occurred in the presence of similar amounts of CBDP, the degree of inhibition differed significantly (50-75% vs. greater than 90%, respectively). These data suggest that there exists in rat serum, a pool of naphthyl ester esterase activity that is very sensitive ex vivo (greater than 90% inhibition) to CBDP and may be very useful in validating a rodent model for soman toxicity.
ESTHER : Chambers_1991_Neurosci.Biobehav.Rev_15_85
PubMedSearch : Chambers_1991_Neurosci.Biobehav.Rev_15_85
PubMedID: 2052204