Malik A

References (20)

Title : Process optimization and characterization of hydrolysate from underutilized brown macroalgae (Padina tetrastromatica) after fucoidan extraction through subcritical water hydrolysis - Hans_2023_J.Environ.Manage_349_119497
Author(s) : Hans N , Solanki D , Nagpal T , Amir H , Naik S , Malik A
Ref : J Environ Manage , 349 :119497 , 2023
Abstract : The growing demand for macroalgal biomass as a source of proteins, peptides, and amino acids is garnering attention for their biological and functional properties. This study depicts the use of emerging green techniques, i.e. subcritical water, to hydrolyze protein from Padina tetrastromatica. The biomass was treated with subcritical water at varying temperatures between 100 and 220 degreesC for 10-40 min at a biomass to water proportion of 1:50 (w/v) and pressure of 4.0 MPa. The optimum conditions for recovering the maximum protein (127.2 +/- 1.1 mg g(-1)), free amino acids (58.4 +/- 1.0 mg g(-1)), highest degree of hydrolysis (58.8 +/- 1.2 %) and low molecular weight peptides (<650 Da) were found to be 220 degreesC for 10 min. The amino acid profiling of the hydrolysate revealed that it contains 45 % essential amino acids, with the highest concentration of methionine (0.18 %), isoleucine (0.12 %) and leucine (0.10 %). It was found that the hydrolysate contains phenolics (23.9 +/- 1.4 mg GAE g(-1)) and flavonoids (1.23 +/- 0.1 mg QE g(-1)), which are largely responsible for antioxidant activity. The hydrolysate effectively inhibits acetylcholinesterase and alpha-amylase in vitro, with IC(50) values of 17.9 +/- 0.1 mg mL(-1) and 16.0 +/- 0.5 %, respectively, which can help prevent Alzheimer's disease and diabetes mellitus. Consequently, this study reveals that utilizing eco-friendly subcritical water hydrolysis method, 79 % of the protein was recovered from P. tetrastromatica, which might be an effective source of bioactive peptides in various nutraceutical, pharmaceutical and cosmeceutical applications.
ESTHER : Hans_2023_J.Environ.Manage_349_119497
PubMedSearch : Hans_2023_J.Environ.Manage_349_119497
PubMedID: 37951112

Title : Pyridostigmine Suicidal Attempt in a Myasthenia Gravis Patient - Malabaey_2019_Am.J.Case.Rep_20_1418
Author(s) : Malabaey MAT , Al-Saud AA , Alaska YA , Almas A , Malik A
Ref : Am J Case Rep , 20 :1418 , 2019
Abstract : BACKGROUND Pyridostigmine is a quaternary amine parasympathomymetic which inhibits acetylcholinesterase for the treatment of various conditions such as myasthenia gravis. Previously, no cases of pyridostigmine toxicity in human beings have been reported except the cases reported among the troops of Persian Gulf War. CASE REPORT A 47-year-old female intentionally ingested a high dose of pyridostigmine (Mestinon) and developed its toxic symptoms within 1 hour of ingestion. She was treated with injections of atropine and pralidoxime. The patient made an excellent recovery and responded to the classical treatment using atropine and pralidoxime. She was discharged on the second day of admission. CONCLUSIONS The authors demonstrated that pyridostigmine poisoning is self-limiting and well tolerated by young adults; however, unwanted effects of pyridostigmine on the heart has still to be considered which may become profound to the point of generating heart failure, syncope, or stress particularly in elderly patients. As the literature on human toxicity with pyridostigmine is scarce, not much data is available on its toxicity. However, prompt and specific management of pyridostigmine toxicity promises safety.
ESTHER : Malabaey_2019_Am.J.Case.Rep_20_1418
PubMedSearch : Malabaey_2019_Am.J.Case.Rep_20_1418
PubMedID: 31554781

Title : Designing of promising medicinal scaffolds for Alzheimer's disease through enzyme inhibition, lead optimization, molecular docking and dynamic simulation approaches - Hassan_2019_Bioorg.Chem_91_103138
Author(s) : Hassan M , Abbasi MA , Aziz Ur R , Siddiqui SZ , Shahzadi S , Raza H , Hussain G , Shah SAA , Ashraf M , Shahid M , Seo SY , Malik A
Ref : Bioorg Chem , 91 :103138 , 2019
Abstract : In the designed research work, a series of 2-furoyl piperazine based sulfonamide derivatives were synthesized as therapeutic agents to target the Alzheimer's disease. The structures of the newly synthesized compounds were characterized through spectral analysis and their inhibitory potential was evaluated against butyrylcholinesterase (BChE). The cytotoxicity of these sulfonamides was also ascertained through hemolysis of bovine red blood cells. Furthermore, compounds were inspected by Lipinki Rule and their binding profiles against BChE were discerned by molecular docking. The protein fluctuations in docking complexes were recognized by dynamic simulation. From our in vitro and in silico results 5c, 5j and 5k were identified as promising lead compounds for the treatment of targeted disease.
ESTHER : Hassan_2019_Bioorg.Chem_91_103138
PubMedSearch : Hassan_2019_Bioorg.Chem_91_103138
PubMedID: 31446329

Title : Bio-sensing of organophosphorus pesticides: A review - Pundir_2019_Biosens.Bioelectron_140_111348
Author(s) : Pundir CS , Malik A , Preety
Ref : Biosensors & Bioelectronics , 140 :111348 , 2019
Abstract : Organophosphorus (OP) pesticides have been used widely as agricultural and household pest control agents for almost five decades and persist in our water resources, fruits, vegetables and processed food as health and environmental hazardous compounds. Thus, detection of these harmful OP pesticides at an ease with high sensitivity and selectivity is the need of hour. Bio-sensing technology meet these requirements and has been employed at a large scale for detection. The present review is aimed mainly to provide the overview of the past and recent advances occurred in the field of biosensor technology employed for the detection of these OP compounds. The review describes the principle and strategy of various OP biosensors including electrochemical (amperometric, potentiometric), thermal, piezoelectric, optical (fluorescence, Surface Plasmon Resonance (SPR)), microbial and DNA biosensors in detail. The electrochemical biosensors are generally, based on inhibition of enzyme, acetyl cholinesterase (AChE), butyryl cholinesterase (BChE), tyrosinase and alkaline phosphatase or enzyme (organophosphorus hydrolase, OPH)) catalyzed reaction. The detection limits and linearity range of various OP biosensors have also been compared. AChE inhibition based amperometric OP biosensors exhibited the lowest detection limit of 1x10(-11)muM with a linearity range of 1.0x10(-11) - 1.0x10(-2)muM.
ESTHER : Pundir_2019_Biosens.Bioelectron_140_111348
PubMedSearch : Pundir_2019_Biosens.Bioelectron_140_111348
PubMedID: 31153016

Title : In-Silico Characterization and in-Vivo Validation of Albiziasaponin-A, Iso-Orientin, and Salvadorin Using a Rat Model of Alzheimer's Disease - Rasool_2018_Front.Pharmacol_9_730
Author(s) : Rasool M , Malik A , Waquar S , Tul-Ain Q , Jafar TH , Rasool R , Kalsoom A , Ghafoor MA , Sehgal SA , Gauthaman K , Naseer MI , Al-Qahtani MH , Pushparaj PN
Ref : Front Pharmacol , 9 :730 , 2018
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia, excessive acetylcholinesterase (AChE) activity, formation of neurotoxic amyloid plaque, and tau protein aggregation. Based on literature survey, we have shortlisted three important target proteins (AChE, COX2, and MMP8) implicated in the pathogenesis of AD and 20 different phytocompounds for molecular docking experiments with these three target proteins. The 3D-structures of AChE, COX2, and MMP8 were predicted by homology modeling by MODELLER and the threading approach by using ITASSER. Structure evaluations were performed using ERRAT, Verify3D, and Rampage softwares. The results based on molecular docking studies confirmed that there were strong interactions of these phytocompounds with AChE, COX2, and MMP8. The top three compounds namely Albiziasaponin-A, Iso-Orientin, and Salvadorin showed least binding energy and highest binding affinity among all the scrutinized compounds. Post-docking analyses showed the following free energy change for Albiziasaponin-A, Salvadorin, and Iso-Orientin (-9.8 to -15.0 kcal/mol) as compared to FDA approved drugs (donepezil, galantamine, and rivastigmine) for AD (-6.6 to -8.2 Kcal/mol) and interact with similar amino acid residues (Pro-266, Asp-344, Trp-563, Pro-568, Tyr-103, Tyr-155, Trp-317, and Tyr-372) with the target proteins. Furthermore, we have investigated the antioxidant and anticholinesterase activity of these top three phytochemicals namely, Albiziasaponin-A, Iso-Orientin, and Salvadorin in colchicine induced rat model of AD. Sprague Dawley (SD) rat model of AD were developed using bilateral intracerebroventricular (ICV) injection of colchicine (15 mug/rat). After the induction of AD, the rats were subjected to treatment with phytochemicals individually or in combination for 3 weeks. The serum samples were further analyzed for biomarkers such as 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), matrix metalloproteinase-8 (MMP-8), isoprostanes-2 alpha (isoP-2alpha), and acetylcholine esterase (AChE) using conventional Enzyme Linked Immunosorbent Assay (ELISA) method. Additionally, the status of lipid peroxidation was estimated calorimetrically by measuring thiobarbituric acid reactive substances (TBARS). Here, we observed a statistically significant reduction (P < 0.05) in the oxidative stress and inflammatory markers in the treatment groups receiving mono and combinational therapies using Albiziasaponin-A, Iso-Orientin, and Salvadorin as compared to colchicine alone group. Besides, the ADMET profiles of these phytocompounds were very promising and, hence, these potential neuroprotective agents may further be taken for preclinical studies either as mono or combinational therapy for AD.
ESTHER : Rasool_2018_Front.Pharmacol_9_730
PubMedSearch : Rasool_2018_Front.Pharmacol_9_730
PubMedID: 30123124

Title : Transcriptomic, biochemical and individual markers in transplanted Daphnia magna to characterize impacts in the field - Rivetti_2015_Sci.Total.Environ_503-504_200
Author(s) : Rivetti C , Campos B , Faria M , De Castro Catala N , Malik A , Munoz I , Tauler R , Soares AM , Osorio V , Perez S , Gorga M , Petrovic M , Mastroianni N , de Alda ML , Masia A , Campo J , Pico Y , Guasc H , Barcelo D , Barata C
Ref : Sci Total Environ , 503-504 :200 , 2015
Abstract : Daphnia magna individuals were transplanted across 12 sites from three Spanish river basins (Llobregat, Ebro, Jucar) showing different sources of pollution. Gene transcription, feeding and biochemical responses in the field were assessed and compared with those obtained in re-constituted water treatments spiked with organic eluates obtained from water samples collected at the same locations and sampling periods. Up to 166 trace contaminants were detected in water and classified by their mode of action into 45 groups that included metals, pharmaceuticals, pesticides, illicit drugs, and other industrial compounds. Physicochemical water parameters differentiated the three river basins with Llobregat having the highest levels of conductivity, metals and pharmaceuticals, followed by Ebro, whereas the Jucar river had the greatest levels of illicit drugs. D. magna grazing rates and cholinesterase activity responded similarly than the diversity of riparian benthic communities. Transcription patterns of 13 different genes encoding for general stress, metabolism and energy processes, molting and xenobiotic transporters corroborate phenotypic responses differentiated sites within and across river basins. Principal Component Analysis and Partial Least Square Projections to Latent Structures regression analyses indicated that measured in situ responses of most genes and biomarkers and that of benthic macroinvertebrate diversity indexes were affected by distinct environmental factors. Conductivity, suspended solids and fungicides were negatively related with the diversity of macroinvertebrates cholinesterase, and feeding responses. Gene transcripts of heat shock protein and metallothionein were positively related with 11 classes of organic contaminants and 6 metals. Gene transcripts related with signaling paths of molting and reproduction, sugar, protein and xenobiotic metabolism responded similarly in field and lab exposures and were related with high residue concentrations of analgesics, diuretics, psychiatric drugs, beta blockers, illicit drugs, trizoles, bisphenol A, caffeine and pesticides. These results indicate that application of omic technologies in the field is a promising subject in water management.
ESTHER : Rivetti_2015_Sci.Total.Environ_503-504_200
PubMedSearch : Rivetti_2015_Sci.Total.Environ_503-504_200
PubMedID: 25005238

Title : Synthesis, characterization and enzyme inhibition study of O-substituted derivatives of chlorinated coumarin - Rehman_2014_Pak.J.Pharm.Sci_27_271
Author(s) : Rehman AU , Magsi S , Abbasi MA , Rasool S , Malik A , Hussain G , Ashraf M , Noreen Khalid NK
Ref : Pak J Pharm Sci , 27 :271 , 2014
Abstract : Coumarins have much importance in dyes, drugs, perfumes and pesticides. In the demonstrated research work, a benignant series of chlorinated coumarins was synthesized and screened against different enzymes. First, 6-Chloro-7-hydroxy-4-methyl-2H-chromen-2-one (3) was geared up by the reaction of 4-chlororesorcinol (1) and ethyl acetoacetate (2) in the presence of concentrated H2SO4. Second, various O-substituted derivatives of chlorinated coumarins, 5a-j, were set up by pairing different alkyl/aralkyl halides, 4a-j, with 3 in the presence of NaH in DMF as solvent. The structures of all the synthesized compounds were clarified through spectral analysis using EI-MS, IR and 1H-NMR. The different enzymes used for the evaluation of bioactivity of all the synthesized compounds were acetyl cholinesterase (AChE), butyryl cholinesterase (BChE) and lipoxygenase (LOX). The most proficient activity was shown against both cholinesterase enzymes.
ESTHER : Rehman_2014_Pak.J.Pharm.Sci_27_271
PubMedSearch : Rehman_2014_Pak.J.Pharm.Sci_27_271
PubMedID: 24577914

Title : Synthesis of some new biologically active N-substituted-2''- [(phenylsulfonyl)(piperidin-1-yl)amino]acetamide derivatives - Khalid_2014_Pak.J.Pharm.Sci_27_517
Author(s) : Khalid H , Rehman AU , Abbasi MA , Siddiqui SZ , Malik A , Ashraf M , Ahmad I , Ejaz SA
Ref : Pak J Pharm Sci , 27 :517 , 2014
Abstract : A new series of N-aryl/aralkyl substitued-2"-[(phenylsulfonyl)(piperidin-1-yl)amino]acetamide (7a-k) was synthesized. These derivatives were geared up by the pairing of benzenesulfonyl chloride (4) with 1-aminopiperidine (5) under dynamic pH control in aqueous media to afford parent compound N-(Piperidin-1-yl) benzenesulfonamide (6), followed by the substitution at nitrogen atom with different electrophiles N-aryl/aralkyl-substituted-2-bromoacetamides (3a-k) in the presence of sodium hydride (NaH) and N,N-Dimethylformamide (DMF) to give a new series of N-substituted derivatives of acetamide (7a-k) bearing piperidine moiety. All the synthesized compounds were confirmed on the basis of IR, EIMS and 1H-NMR spectral data. The synthesized compounds were evaluated against acetylcholinesterase and butyrylcholinesterase (AChE and BChE) respectively and lipoxygenase (LOX) enzymes. Almost all the synthesized compounds displayed promising activity but few of them remained inactive against lipoxygenase enzymes.
ESTHER : Khalid_2014_Pak.J.Pharm.Sci_27_517
PubMedSearch : Khalid_2014_Pak.J.Pharm.Sci_27_517
PubMedID: 24811811

Title : New butyrylcholinesterase inhibitory steroid and peroxy acid from Leucas urticifolia - Fatima_2008_Arch.Pharm.Res_31_999
Author(s) : Fatima I , Ahmad I , Anis I , Malik A , Afza N , Iqbal L , Latif M
Ref : Arch Pharm Res , 31 :999 , 2008
Abstract : A new steroid leucisterol (1) and a new peroxy acid urticic acid (2) along with methoxybenzyl benzoate (3), 4-hydroxy benzoic acid (4), beta-sitosterol (5), and ursolic acid (6), have been isolated from the chloroform soluble fraction of the whole plant of Leucas urticifolia. Their structures were elucidated on the basis of nuclear magnetic resonance (1D and 2D NMR) spectral data. Leucisterol showed potent inhibitory activity against butyrylcholinesterase enzyme.
ESTHER : Fatima_2008_Arch.Pharm.Res_31_999
PubMedSearch : Fatima_2008_Arch.Pharm.Res_31_999
PubMedID: 18787788

Title : Leufolins A and B, potent butyrylcholinesterase-inhibiting flavonoid glucosides from Leucas urticifolia - Atia_2007_Molecules_12_1447
Author(s) : Atia tun N , Fatima I , Ahmad I , Malik A , Afza N , Iqbal L , Latif M , Khan SB
Ref : Molecules , 12 :1447 , 2007
Abstract : New flavonoidal glucosides leufolins A (1) and B (2), have been isolated from the ethyl acetate soluble fraction of the whole plants of Leucas urticifolia. Their structures were elucidated on the basis of extensive analysis of nuclear magnetic resonance (1D and 2D NMR) spectral data. Both of these compounds exhibited significant inhibitory potential against the enzyme butyrylcholinesterase.
ESTHER : Atia_2007_Molecules_12_1447
PubMedSearch : Atia_2007_Molecules_12_1447
PubMedID: 17909500

Title : Isolation and enzyme-inhibition studies of the chemical constituents from Ajuga bracteosa - Riaz_2007_Chem.Biodivers_4_72
Author(s) : Riaz N , Nawaz SA , Mukhtar N , Malik A , Afza N , Ali S , Ullah S , Muhammad P , Choudhary MI
Ref : Chem Biodivers , 4 :72 , 2007
Abstract : Bractin A (=(2S,3S,4R,5E)-2-{[(2R)-2-hydroxydodecanoyl]amino}triacont-5-ene-1,3,4-triol; 1) and bractin B (=(2S,3S,4R,5E,8E)-2-{[(2R)-2-hydroxyhexacosanoyl]amino}pentadeca-5,8-diene-3,4,1 5-triol 1-O-beta-D-glucopyranoside; 2), new sphingolipids, and bractic acid (=(5Z,10Z,15Z)-2-decyl-4,7,8,12,13,17,18-heptahydroxy-20,23-dioxopentacosa-5,10,1 5-trienoic acid; 3), a long-chain polyhydroxy acid, were isolated from the whole plant Ajuga bracteosa along with four known diterpenoids 4-7. Their structures were deduced by spectral studies including 1D- and 2D-NMR spectroscopy. Compounds 1-3 displayed inhibitory potential against enzyme lipoxygenase, while compounds 4-7 inhibited cholinesterase enzymes in a concentration-dependent manner with IC(50) values in the range 10.0-33.0, 14.0-35.2, and 10.0-19.0 microM for lipoxygenase, acetylcholinesterase, and butyrylcholinesterase, respectively. Lineweaver-Burk, and Dixon plots, and their secondary replots indicated that all compounds exhibit non-competitive type of inhibition with K(i) values in the range of 9.5-35.2, 15.2-36.0, and 11.6-20.5 microM, for lipoxygenase, acetylcholinesterase, and butyrylcholinesterase, respectively.
ESTHER : Riaz_2007_Chem.Biodivers_4_72
PubMedSearch : Riaz_2007_Chem.Biodivers_4_72
PubMedID: 17256736

Title : New butyrylcholinesterase inhibitory triterpenes from Salvia santolinifolia - Mehmood_2006_Arch.Pharm.Res_29_195
Author(s) : Mehmood S , Riaz N , Nawaz SA , Afza N , Malik A , Choudhary MI
Ref : Arch Pharm Res , 29 :195 , 2006
Abstract : Slavins A (1) and B (2), the new amyrin type triterpenes, have been isolated from the chloroform soluble fraction of Salvia santolinifolia and assigned structures on the basis of spectral studies including 2D NMR. Both the compounds displayed inhibitory potential against the enzyme butyrylcholinesterase.
ESTHER : Mehmood_2006_Arch.Pharm.Res_29_195
PubMedSearch : Mehmood_2006_Arch.Pharm.Res_29_195
PubMedID: 16596990

Title : Isolation and cholinesterase-inhibition studies of sterols from Haloxylon recurvum - Ahmed_2006_Bioorg.Med.Chem.Lett_16_573
Author(s) : Ahmed E , Nawaz SA , Malik A , Choudhary MI
Ref : Bioorganic & Medicinal Chemistry Lett , 16 :573 , 2006
Abstract : Haloxysterols A-D (1-4), new C-24 alkylated sterols, have been isolated from the chloroform soluble fraction of Haloxylon recurvum, along with five known sterols 5-9, which are reported for the first time from this species. Their structures were determined by means of 1D- and 2D-NMR techniques. Compounds 1-9 inhibited cholinesterase enzymes in a concentration-dependent manner with K(i) values ranging between 0.85-25.5 and 1.0-19.0 microM against acetylcholinesterase (AChE; EC and butyrylcholinesterase (BChE; EC enzymes, respectively. Lineweaver-Burk, Dixon plots and their secondary replots indicated that compounds 1-9 are non-competitive inhibitors of both AChE and BChE enzymes.
ESTHER : Ahmed_2006_Bioorg.Med.Chem.Lett_16_573
PubMedSearch : Ahmed_2006_Bioorg.Med.Chem.Lett_16_573
PubMedID: 16274989

Title : Phenolic constituents from Perovskia atriplicifolia - Perveen_2006_Nat.Prod.Res_20_347
Author(s) : Perveen S , Khan SB , Malik A , Tareen RB , Nawaz SA , Choudhary MI
Ref : Nat Prod Res , 20 :347 , 2006
Abstract : Perovskoate, an isorinic acid derivative (1) and perovskoside, the catechol derivative (2) have been isolated from the ethyl acetate soluble fraction of the whole plant of Perovskia atriplicifolia and assigned the structure 3(7-hydroxyphenyl)-2-hydroxy propanoic acid; (R)-form, 2-O-(6',7'-dihydroxy-E-cinnamoyl) (1) and 2-methoxy-4-(undecyl-4'-O-beta-D-glucopyranosyl) phenol (2). In addition, caffeic acid (3) and ferulic acid (4) have been reported for the first time from this species. The structures of these compounds were assigned on the basis of 1D and 2D NMR techniques. The compound 1 showed significant inhibitory activity against lipoxygenase and weak to moderate activity against cholinesterases.
ESTHER : Perveen_2006_Nat.Prod.Res_20_347
PubMedSearch : Perveen_2006_Nat.Prod.Res_20_347
PubMedID: 16644529

Title : Butyrylcholinesterase inhibitory guaianolides from Amberboa ramosa - Khan_2005_Arch.Pharm.Res_28_172
Author(s) : Khan SB , Azhar Ul H , Perveen S , Afza N , Malik A , Nawaz SA , Shah MR , Choudhary MI
Ref : Arch Pharm Res , 28 :172 , 2005
Abstract : Phytochemical investigation of the whole plant of Amberboa ramosa led to the isolation of six sesquiterpene lactones which could be identified as 8alpha-hydroxy-11beta-methyl-1alphaH, 5alphaH, 6betaH, 7alphaH, 11alphaH-guai-10(14), 4(15)-dien-6, 12-olide(1), 3beta, 8alpha-dihydroxy-11alpha-methyl-1alphaH, 5alphaH, 6betaH, 7alphaH, 11betaH-guai-10(14), 4 (15)-dien-6, 12-olide (2), 3beta, 4alpha, 8alpha-trihydroxy-4beta-(hydroxymethyl)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14), 11(13)-dien-6, 12-olide (3), 3beta, 4alpha, 8alpha-trihydroxy-4beta-(chloromethyl)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14),11(13)-dien-6, 12-olide(4), 3beta, 4alpha, dihydroxy-4beta-(hydroxymethyl)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14),11(13)-dien-6, 12-olide(5), 3beta, 4alpha-dihydroxy-4beta-(chloromethyl)-8alpha-(4-hydroxymethacrylate)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14),11 (13)-dien-6,12-olide (6) by spectroscopic methods. All of them showed inhibitory potential against butyrylcholinesterase.
ESTHER : Khan_2005_Arch.Pharm.Res_28_172
PubMedSearch : Khan_2005_Arch.Pharm.Res_28_172
PubMedID: 15789746

Title : Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties - Choudhary_2005_Biochem.Biophys.Res.Commun_334_276
Author(s) : Choudhary MI , Nawaz SA , Ul-Haq Z , Lodhi MA , Ghayur MN , Jalil S , Riaz N , Yousuf S , Malik A , Gilani AH , ur-Rahman A
Ref : Biochemical & Biophysical Research Communications , 334 :276 , 2005
Abstract : The withanolides 1-3 and 4-5 isolated from Ajuga bracteosa and Withania somnifera, respectively, inhibited acetylcholinesterase (AChE, EC and butyrylcholinesterase (BChE, EC enzymes in a concentration-dependent fashion with IC50 values ranging between 20.5 and 49,2 microm and 29.0 and 85.2 microm for AChE and BChE, respectively. Lineweaver-Burk as well as Dixon plots and their secondary replots indicated that compounds 1, 3, and 5 are the linear mixed-type inhibitors of AChE, while 2 and 4 are non-competitive inhibitors of AChE with K(i) values ranging between 20.0 and 45.0 microm. All compounds were found to be non-competitive inhibitors of BChE with K(i) values ranging between 27.7 and 90.6 microm. Molecular docking study revealed that all the ligands are completely buried inside the aromatic gorge of AChE, while compounds 1, 3, and 5 extend up to the catalytic triad. A comparison of the docking results showed that all ligands generally adopt the same binding mode and lie parallel to the surface of the gorge. The superposition of the docked structures demonstrated that the non-flexible skeleton of the ligands always penetrates the aromatic gorge through the six-membered ring A, allowing their simultaneous interaction with more than one subsite of the active center. The affinity of ligands with AChE was found to be the cumulative effects of number of hydrophobic contacts and hydrogen bonding. Furthermore, all compounds also displayed dose-dependent (0.005-1.0 mg/mL) spasmolytic and Ca2+ antagonistic potentials in isolated rabbit jejunum preparations, compound 4 being the most active with an ED50 value of 0.09 +/- 0.001 mg/mL and 0.22 +/- 0.01 microg/mL on spontaneous and K+ -induced contractions, respectively. The cholinesterase inhibitory potential along with calcium antagonistic ability and safe profile in human neutrophil viability assay could make compounds 1-5 possible drug candidates for further study to treat Alzheimer's disease and associated problems.
ESTHER : Choudhary_2005_Biochem.Biophys.Res.Commun_334_276
PubMedSearch : Choudhary_2005_Biochem.Biophys.Res.Commun_334_276
PubMedID: 16108094

Title : Haloxylines A and B, antifungal and cholinesterase inhibiting piperidine alkaloids from Haloxylon salicornicum - Ferheen_2005_Chem.Pharm.Bull.(Tokyo)_53_570
Author(s) : Ferheen S , Ahmed E , Afza N , Malik A , Shah MR , Nawaz SA , Choudhary MI
Ref : Chem Pharm Bull (Tokyo) , 53 :570 , 2005
Abstract : Haloxylines A (1) and B (2), new piperidine alkaloids, have been isolated from the chloroform soluble fraction of Haloxylon salicornicum and their structures elucidated by spectroscopic techniques including 2D-NMR. Both the compounds displayed antifungal and cholinesterase enzymes inhibitory potentials.
ESTHER : Ferheen_2005_Chem.Pharm.Bull.(Tokyo)_53_570
PubMedSearch : Ferheen_2005_Chem.Pharm.Bull.(Tokyo)_53_570
PubMedID: 15863932

Title : Cholinesterase-inhibiting withanolides from Ajuga bracteosa - Riaz_2004_Chem.Biodivers_1_1289
Author(s) : Riaz N , Malik A , Nawaz SA , Muhammad P , Choudhary MI
Ref : Chem Biodivers , 1 :1289 , 2004
Abstract : Three new withanolides, bracteosin A (= (22R)-5beta,6beta : 22,26-diepoxy-4beta,28-dihydroxy-3beta-methoxyergost-24-ene-1,26-dione; 1), bracteosin B (= (22R)-5beta,6beta : 22,26-diepoxy-4beta,28-dihydroxy-3beta-methoxy-1,26-dioxoergost-24-en-19-oic acid; 2), and bracteosin C (= (22R)-22,26-epoxy-4beta,6beta,27-trihydroxy-3beta-methoxyergost-24-ene-1,26-dione ; 3), have been isolated from the whole plants of Ajuga bracteosa. Their structures were deduced by spectral analysis, including 1D- and 2D-NMR techniques. In addition, dihydroclerodin-1, clerodinin A, lupulin A, and dihydroajugapitin have also been isolated for the first time from this species. Compounds 1-3 exhibited evident inhibitory potential against cholinesterase enzymes in a concentration-dependent fashion.
ESTHER : Riaz_2004_Chem.Biodivers_1_1289
PubMedSearch : Riaz_2004_Chem.Biodivers_1_1289
PubMedID: 17191906

Title : Enzyme inhibiting lignans from Vitex negundo - Azhar_2004_Chem.Pharm.Bull.(Tokyo)_52_1269
Author(s) : Azhar Ul H , Malik A , Anis I , Khan SB , Ahmed E , Ahmed Z , Nawaz SA , Choudhary MI
Ref : Chem Pharm Bull (Tokyo) , 52 :1269 , 2004
Abstract : Two new lignans trivially named negundins A (1) and B (2), were isolated along with (+)-diasyringaresinol (3), (+)-lyoniresinol (4), vitrofolal E (5) and vitrofolal F (6), reported for the first time from this species. The structures of the new compounds were established through spectral studies. Compound 2 showed potent inhibitory activity against lipoxygenase enzyme, while 5 showed moderate activity against butyryl-cholinesterase.
ESTHER : Azhar_2004_Chem.Pharm.Bull.(Tokyo)_52_1269
PubMedSearch : Azhar_2004_Chem.Pharm.Bull.(Tokyo)_52_1269
PubMedID: 15520511

Title : Cholinesterase Inhibitory Constituents from Onosma hispida - Ahmad_2003_Chem.Pharm.Bull.(Tokyo)_51_412
Author(s) : Ahmad I , Anis I , Malik A , Nawaz SA , Choudhary MI
Ref : Chem Pharm Bull (Tokyo) , 51 :412 , 2003
Abstract : Hispidone, a new flavanone, has been isolated from Onosma hispida and assigned the structure (2S)-5,2'-dihydroxy-7,4',5'-trimethoxyflavanone (1) by spectroscopic methods. In addition, (2S)-5,2'-dihydroxy-7,5'-dimethoxyflavanone (2), benzoic acid (3), and 4-hydroxy benzoic acid (4) are also reported for the first time from this species.
ESTHER : Ahmad_2003_Chem.Pharm.Bull.(Tokyo)_51_412
PubMedSearch : Ahmad_2003_Chem.Pharm.Bull.(Tokyo)_51_412
PubMedID: 12672994