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Discovery of dihydrochalcone as potential lead for Alzheimer's disease: in silico and in vitro study.

ABSTRACT: By the virtual screening method we have screened out Dihydrochalcone as a top-lead for the Alzheimer's disease using the database of about 32364 natural compounds. The binding affinity of this ligand to amyloid beta (A?) fibril has been thoroughly studied by computer simulation and experiment. Using the Thioflavin T (ThT) assay we have obtained the inhibition constant IC50 ?M. This result is in good agreement with the estimation of the binding free energy obtained by the molecular mechanic-Poisson Boltzmann surface area method and all-atom simulation with the force field CHARMM 27 and water model TIP3P. Cell viability assays indicated that Dihydrochalcone could effectively reduce the cytotoxicity induced by A?. Thus, both in silico and in vitro studies show that Dihydrochalcone is a potential drug for the Alzheimers disease.

SUBMITTER: Viet MH

PROVIDER: S-EPMC3832475 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Discovery of dihydrochalcone as potential lead for Alzheimer's disease: in silico and in vitro study.

Viet Man Hoang MH Chen Chun-Yu CY Hu Chin-Kun CK Chen Yun-Ru YR Li Mai Suan MS

PloS one 20131118 11

By the virtual screening method we have screened out Dihydrochalcone as a top-lead for the Alzheimer's disease using the database of about 32364 natural compounds. The binding affinity of this ligand to amyloid beta (Aβ) fibril has been thoroughly studied by computer simulation and experiment. Using the Thioflavin T (ThT) assay we have obtained the inhibition constant IC50 μM. This result is in good agreement with the estimation of the binding free energy obtained by the molecular mechanic-Poiss ...[more]

PMID: 24260164

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Project description:UnlabelledAcetylcholine-esterase (AchE) inhibitors are one of the most potent drug molecules against Alzheimer's disease (AD). But, patients treated with current AchE inhibitors often experience severe side effects. Quercetin is a plant flavonoid compound which can act as AchE inhibitor and it may be a better alternative to current AchE inhibitors in terms of effectiveness with no or fewer side effects.AimsThe aim of the study was to compare quercetin with conventional AchE inhibitors to search for a better drug candidate.Methods and materialsPhysico-chemical properties of conventional drugs and quercetin were predicted using bioinformatics tools. Molecular docking of these compounds on the active site of AchE was performed using AutoDock and comparative analysis was performed. Later, modification on the basic structure of quercetin with different functional groups was done to perform QSAR analysis.Result and discussionQuercetin showed a similar drug likeness score to the conventional drugs. The binding strength for quercetin in the active site of the enzyme was -8.8 kcal/mol, which was considerably higher than binding scores for some of the drugs such as donepezil (binding score -7.9 kcal/mol). Fifteen hydrogen bonds were predicted between quercetin and the enzyme whereas conventional drugs had fewer or even no hydrogen bonds. It implies that quercetin can act as a better inhibitor than conventional drugs. To find out even better inhibitor, similar structures of quercetin were searched through SIMCOMP database and a methylation in the 4-OH position of the molecule showed better binding affinity than parent quercetin. Quantitative structure activity relationship study indicated that O-4 methylation was specifically responsible for better affinity.ConclusionThis in silico study has conclusively predicted the superiority of the natural compound quercetin over the conventional drugs as AchE inhibitor and it sets the need for further in-vitro study of this compound in future.

Dataset Information

Discovery of dihydrochalcone as potential lead for Alzheimer's disease: in silico and in vitro study.

Publications

Discovery of dihydrochalcone as potential lead for Alzheimer's disease: in silico and in vitro study.

Similar Datasets

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