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BioMed Research International
Volume 2014 (2014), Article ID 979606, 12 pages
Research Article

Development of Dual Inhibitors against Alzheimer’s Disease Using Fragment-Based QSAR and Molecular Docking

1Apaji Institute of Mathematics & Applied Computer Technology, Banasthali University, Tonk, Rajasthan 304022, India
2School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India
3Department of Biochemistry, University of Kashmir, Srinagar 190006, India

Received 17 December 2013; Revised 27 March 2014; Accepted 27 March 2014; Published 12 June 2014

Academic Editor: Jason E. Mcdermott

Copyright © 2014 Manisha Goyal et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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. -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 (EDC and FDC) which showed significant binding affinity for BACE-1 and AChE. This study paves way for consideration of these lead molecules as prospective drugs for the effective dual inhibition of BACE-1 and AChE. The GQSAR model provides site-specific clues about the molecules where certain modifications can result in increased biological activity. This information could be of high value for design and development of multifunctional drugs for combating AD.