Khare SK

References (9)

Title : Screening of Multitarget-Directed Natural Compounds as Drug Candidates for Alzheimer's Disease Using In Silico Techniques: Their Extraction and In Vitro Validation - Srivastava_2023_ACS.Omega_8_38118
Author(s) : Srivastava S , Sharma S , Deep S , Khare SK
Ref : ACS Omega , 8 :38118 , 2023
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder that impairs neurocognitive function. Acetylcholinesterase (AChE) and beta-site APP cleaving enzyme 1 (BACE1) are the two main proteins implicated in AD. Indeed, the major available commercial drugs (donepezil, rivastigmine, and galantamine) against Alzheimer's are AChE inhibitors. However, none of these drugs are known to reverse or reduce the pathophysiological condition of the disease since there are multiple contributing factors to AD. Therefore, there is a need to develop a multitarget-directed ligand approach for its treatment. In the present study, plant bioactive compounds were screened for their AChE and BACE1 inhibition potential by conducting molecular docking studies. Considering their docking score and pharmacokinetic properties, limonin, peimisine, serratanine B, and withanolide A were selected as the lead compounds. Molecular dynamics simulations of these protein-ligand complexes confirmed the conformational and energetically stabilized enzyme-inhibitor complexes. The inhibition potential of the lead compounds was validated by in vitro enzyme assay. Withanolide A inhibited AChE (IC(50) value of 107 microM) and showed mixed-type inhibition. At this concentration, it inhibited BACE1 activity by 57.10% and was stated as most effective. Both the compounds, as well as their crude extracts, were found to have no cytotoxic effect on the SH-SY5Y cell line.
ESTHER : Srivastava_2023_ACS.Omega_8_38118
PubMedSearch : Srivastava_2023_ACS.Omega_8_38118
PubMedID: 37867692

Title : Alzheimer's disease and its treatment by different approaches: A review - Srivastava_2021_Eur.J.Med.Chem_216_113320
Author(s) : Srivastava S , Ahmad R , Khare SK
Ref : Eur Journal of Medicinal Chemistry , 216 :113320 , 2021
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder that impairs mental ability development and interrupts neurocognitive function. This neuropathological condition is depicted by neurodegeneration, neural loss, and development of neurofibrillary tangles and Abeta plaques. There is also a greater risk of developing AD at a later age for people with cardiovascular diseases, hypertension and diabetes. In the biomedical sciences, effective treatment for Alzheimer's disease is a severe obstacle. There is no such treatment to cure Alzheimer's disease. The drug present in the market show only symptomatic relief. The cause of Alzheimer's disease is not fully understood and the blood-brain barrier restricts drug efficacy are two main factors that hamper research. Stem cell-based therapy has been seen as an effective, secure, and creative therapeutic solution to overcoming AD because of AD's multifactorial nature and inadequate care. Current developments in nanotechnology often offer possibilities for the delivery of active drug candidates to address certain limitations. The key nanoformulations being tested against AD include polymeric nanoparticles (NP), inorganic NPs and lipid-based NPs. Nano drug delivery systems are promising vehicles for targeting several therapeutic moieties by easing drug molecules' penetration across the CNS and improving their bioavailability. In this review, we focus on the causes of the AD and their treatment by different approaches.
ESTHER : Srivastava_2021_Eur.J.Med.Chem_216_113320
PubMedSearch : Srivastava_2021_Eur.J.Med.Chem_216_113320
PubMedID: 33652356

Title : Enzymatic Remediation of Polyethylene Terephthalate (PET)-Based Polymers for Effective Management of Plastic Wastes: An Overview - Maurya_2020_Front.Bioeng.Biotechnol_8_602325
Author(s) : Maurya A , Bhattacharya A , Khare SK
Ref : Front Bioeng Biotechnol , 8 :602325 , 2020
Abstract : Globally, plastic-based pollution is now recognized as one of the serious threats to the environment. Among different plastics, polyethylene terephthalate (PET) occupies a pivotal place, its excess presence as a waste is a major environmental concern. Mechanical, thermal, and chemical-based treatments are generally used to manage PET pollution. However, these methods are usually expensive or generate secondary pollutants. Hence, there is a need for a cost-effective and environment-friendly method for efficient management of PET-based plastic wastes. Considering this, enzymatic treatment or recycling is one of the important methods to curb PET pollution. In this regard, PET hydrolases have been explored for the treatment of PET wastes. These enzymes act on PET and end its breakdown into monomeric units and subsequently results in loss of weight. However, various factors, specifically PET crystallinity, temperature, and pH, are known to affect this enzymatic process. For effective hydrolysis of PET, high temperature is required, which facilitates easy accessibility of substrate (PET) to enzymes. However, to function at this high temperature, there is a requirement of thermostable enzymes. The thermostability could be enhanced using glycosylation, immobilization, and enzyme engineering. Furthermore, the use of surfactants, additives such as Ca(2+), Mg(2+), and hydrophobins (cysteine-rich proteins), has also been reported to enhance the enzymatic PET hydrolysis through facilitating easy accessibility of PET polymers. The present review encompasses a brief overview of the use of enzymes toward the management of PET wastes. Various methods affecting the treatment process and different constraints arising thereof are also systematically highlighted in the review.
ESTHER : Maurya_2020_Front.Bioeng.Biotechnol_8_602325
PubMedSearch : Maurya_2020_Front.Bioeng.Biotechnol_8_602325
PubMedID: 33330434

Title : Stability and structure of Penicillium chrysogenum lipase in the presence of organic solvents - Sadaf_2018_Prep.Biochem.Biotechnol__1
Author(s) : Sadaf A , Grewal J , Jain I , Kumari A , Khare SK
Ref : Preparative Biochemistry & Biotechnology , :1 , 2018
Abstract : The present work describes the enzymatic properties of Penicillium chrysogenum lipase and its behavior in the presence of organic solvents. The temperature and pH optima of the purified lipase was found to be 55 degrees C and pH 8.0 respectively. The lipase displayed remarkable stability in both polar and non-polar solvents upto 50% (v/v) concentrations for 72 h. A structural perspective of the purified lipase in different organic solvents was gained by using circular dichroism and intrinsic fluorescence spectroscopy. The native lipase consisted of a predominant alpha-helix structure which was maintained in both polar and non-polar solvents with the exception of ethyl butyrate where the activity was decreased and the structure was disrupted. The quenching of fluorescence intensity in the presence of organic solvents indicated the transformation of the lipase microenviroment P. chrysogenum lipase offers an interesting system for understanding the solvent stability mechanisms which could be used for rationale designing of engineered lipase biocatalysts for application in organic synthesis in non-aqueous media.
ESTHER : Sadaf_2018_Prep.Biochem.Biotechnol__1
PubMedSearch : Sadaf_2018_Prep.Biochem.Biotechnol__1
PubMedID: 30461349

Title : Lipase-catalyzed production of a bioactive fatty amide derivative of 7,10-dihydroxy-8(E)-octadecenoic acid - Khare_2009_Bioresour.Technol_100_1482
Author(s) : Khare SK , Kumar A , Kuo TM
Ref : Bioresour Technol , 100 :1482 , 2009
Abstract : Enzymatic syntheses of fatty amides are of considerable interest due to their wide ranging industrial applications in detergents, shampoo, cosmetics and surfactant formulations. Amidation reaction of Candida antarctica lipase B (CALB) was investigated for direct amidation of carboxylic acid in organic solvent. CALB-mediated production of a novel secondary amide was carried out by reacting the hydroxy oleic acid derivative, 7,10-dihydroxy-8(E)-octadecenoic acid (DOD), with N-methylethanol amine in organic solvent medium. A single, new product peak corresponding to the secondary amide of DOD (D2AM) was detected by high-performance liquid chromatography and thin-layer chromatography. The production of D2AM was achieved in high yields (95%) after 72 h at 50 degrees C in a CALB-catalyzed reaction that contained 100 IU enzyme activity, 50 mM DOD, and 100 mM N-methylethanol amine in isoamyl alcohol. The new fatty amide D2AM displayed potent antimicrobial activity towards Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative bacteria (Proteus vulgaris and Klebsiella pneumonae). D2AM also exhibited antioxidative activity by its alpha,alpha-diphenyl-beta-picryl-hydrazyl (DPPH) radicals scavenging effects.
ESTHER : Khare_2009_Bioresour.Technol_100_1482
PubMedSearch : Khare_2009_Bioresour.Technol_100_1482
PubMedID: 18793843

Title : Cellular response mechanisms in Pseudomonas aeruginosa PseA during growth in organic solvents - Gaur_2009_Lett.Appl.Microbiol_49_372
Author(s) : Gaur R , Khare SK
Ref : Lett Appl Microbiol , 49 :372 , 2009
Abstract : AIMS: Solvent-tolerant bacteria have emerged as a new class of micro-organisms able to grow at high concentrations of toxic solvents. Such bacteria and their solvent-stable enzymes are perceived to be useful for biotransformations in nonaqueous media. In the present study, the solvent-responsive features of a lipase-producing, solvent-tolerant strain Pseudomonas aeruginosa PseA have been investigated to understand the cellular mechanisms followed under solvent-rich conditions. METHODS AND RESULTS: The solvents, cyclohexane and tetradecane with differing log P-values (3.2 and 7.6 respectively), have been used as model systems. Effect of solvents on (i) the cell morphology and structure (ii) surface hydrophobicity and (iii) permeability of cell membrane have been examined using transmission electron microscopy, atomic force microscopy and other biochemical techniques. The results show that (i) less hydrophobic (low log P-value) solvent cyclohexane alters the cell membrane integrity and (ii) cells adapt to organic solvents by changing morphology, size, permeability and surface hydrophobicity. However, no such changes were observed in the cells grown in tetradecane. CONCLUSIONS: It may be concluded that P. aeruginosa PseA responds differently to solvents of different hydrophobicities. Bacterial cell membrane is more permeable to less hydrophobic solvents that eventually accumulate in the cytoplasm, while highly hydrophobic solvents have lesser tendency to access the membrane. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, these are first time observations that show that way of bacterial solvent adaptability depends on nature of solvent. Difference in cellular responses towards solvents of varying log P-values (hydrophobicity) might prove useful to search for a suitable solvent for carrying out whole-cell biocatalysis.
ESTHER : Gaur_2009_Lett.Appl.Microbiol_49_372
PubMedSearch : Gaur_2009_Lett.Appl.Microbiol_49_372
PubMedID: 19712193

Title : Lipase from solvent tolerant Pseudomonas aeruginosa strain: production optimization by response surface methodology and application - Ruchi_2008_Bioresour.Technol_99_4796
Author(s) : Ruchi G , Anshu G , Khare SK
Ref : Bioresour Technol , 99 :4796 , 2008
Abstract : Solvent tolerant Pseudomonas aeruginosa strain PseA has been studied for lipase activity. This strain has earlier been reported to be secreting alkaline and solvent stable protease. It produced an extra cellular lipase with suitable properties for detergent applications viz. (i) alkaline in nature, (ii) stability and compatibility towards bleach oxidants, surfactants and detergent formulations and (iii) resistant to proteolysis. Since the culture supernatant contains both protease and lipase which are together required in detergent formulations, enzymes from P. aeruginosa seem ideal for use as detergent additive. P. aeruginosa lipase exhibited remarkable stability in wide range of organic solvents at 25% (v/v) concentration. This property can be useful for solvent bioremediation and biotransformations in non-aqueous media. Media optimization for cost effective production of lipase was carried out by response surface methodology which led to 5.58-fold increase in lipase production (4580 IU/ml) over un-optimized media.
ESTHER : Ruchi_2008_Bioresour.Technol_99_4796
PubMedSearch : Ruchi_2008_Bioresour.Technol_99_4796
PubMedID: 17976982

Title : Production of protease and lipase by solvent tolerant Pseudomonas aeruginosa PseA in solid-state fermentation using Jatropha curcas seed cake as substrate - Mahanta_2008_Bioresour.Technol_99_1729
Author(s) : Mahanta N , Gupta A , Khare SK
Ref : Bioresour Technol , 99 :1729 , 2008
Abstract : Deoiled Jatropha seed cake was assessed for its suitability as substrate for enzyme production by solid-state fermentation (SSF). Solvent tolerant Pseudomonas aeruginosa PseA strain previously reported by us was used for fermentation. The seed cake supported good bacterial growth and enzyme production (protease, 1818 U/g of substrate and lipase, 625 U/g of substrate) as evident by its chemical composition. Maximum protease and lipase production was observed at 50% substrate moisture, a growth period of 72 and 120 h, and a substrate pH of 6.0 and 7.0, respectively. Enrichment with maltose as carbon source increased protease and lipase production by 6.3- and 1.6-fold, respectively. Nitrogen supplementation with peptone for protease and NaNO(3) for lipase production also enhanced the enzyme yield reaching 11,376 U protease activity and 1084 U lipase activity per gram of Jatropha seed cake. These results demonstrated viable approach for utilization of this huge biomass by solid-state fermentation for the production of industrial enzymes. This offers significant benefit due to low cost and abundant availability of cake during biodiesel production.
ESTHER : Mahanta_2008_Bioresour.Technol_99_1729
PubMedSearch : Mahanta_2008_Bioresour.Technol_99_1729
PubMedID: 17509877

Title : Protein-coated microcrystals of Pseudomonas aeruginosa PseA lipase - Gaur_2008_Appl.Biochem.Biotechnol_151_160
Author(s) : Gaur R , Gupta GN , Vamsikrishnan M , Khare SK
Ref : Appl Biochem Biotechnol , 151 :160 , 2008
Abstract : Highly active Pseudomonas aeruginosa lipase protein-coated microcrystals (PAL PCMC) have been prepared by immobilization of protein onto K(2)SO(4) as excipient solid support carrier and n-propanol as precipitating solvent. Transmission electron micrographs confirmed the formation of PAL PCMC. These PCMC were found to be a catalytically more active and stable preparation for p-nitrophenyl palmitate hydrolysis in n-heptane, compared to free lipase. The V (max), K (m), and temperature optimum for PAL PCMC increased from 0.49 to 5.66 nmol min(-1) mg(-1), 589 to 679.8 mmol, and 40 degrees C to 45 degrees C, respectively. These were thermally more stable with 4.65, 2.56, and 1.24-fold improvement in half lives at 45 degrees C, 55 degrees C, and 60 degrees C compared to free P. aeruginosa PseA lipase. Their catalytic efficiency was enhanced by tenfold over that of free enzyme. PAL PCMC offer a simple and effective technique for obtaining stable and efficient lipase preparation for biocatalysis in nonaqueous medium.
ESTHER : Gaur_2008_Appl.Biochem.Biotechnol_151_160
PubMedSearch : Gaur_2008_Appl.Biochem.Biotechnol_151_160
PubMedID: 18690417