Development of dual inhibitors against Alzheimer's disease using fragment-based QSAR and molecular docking.

ABSTRACT: Alzheimer's (AD) is the leading cause of dementia among elderly people. Considering the complex heterogeneous etiology of AD, there is an urgent need to develop multitargeted drugs for its suppression. β-amyloid cleavage enzyme (BACE-1) and acetylcholinesterase (AChE), being important for AD progression, have been considered as promising drug targets. In this study, a robust and highly predictive group-based QSAR (GQSAR) model has been developed based on the descriptors calculated for the fragments of 20 1,4-dihydropyridine (DHP) derivatives. A large combinatorial library of DHP analogues was created, the activity of each compound was predicted, and the top compounds were analyzed using refined molecular docking. A detailed interaction analysis was carried out for the top two compounds (ED

SUBMITTER: Goyal M 

PROVIDER: S-EPMC4075005 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature