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BioMed Research International
Volume 2013 (2013), Article ID 306081, 15 pages
Research Article

Pharmacophore Modeling and Docking Studies on Some Nonpeptide-Based Caspase-3 Inhibitors

1Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar, Madhya Pradesh 470003, India
2Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835 215, India

Received 26 April 2013; Revised 23 July 2013; Accepted 23 July 2013

Academic Editor: Gjumrakch Aliev

Copyright © 2013 Simant Sharma 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.


Neurodegenerative disorders are major consequences of excessive apoptosis caused by a proteolytic enzyme known as caspase-3. Therefore, caspase-3 inhibition has become a validated therapeutic approach for neurodegenerative disorders. We performed pharmacophore modeling on some synthetic derivatives of caspase-3 inhibitors (pyrrolo[3,4-c]quinoline-1,3-diones) using PHASE 3.0. This resulted in the common pharmacophore hypothesis AAHRR.6 which might be responsible for the biological activity: two aromatic rings (R) mainly in the quinoline nucleus, one hydrophobic (H) group (CH3), and two acceptor (A) groups (–C=O). After identifying a valid hypothesis, we also developed an atom-based 3D-QSAR model applying the PLS algorithm. The developed model was statistically robust ( ; pred_ ). Additionally, we have performed molecular docking studies, cross-validated our results, and gained a deeper insight into its molecular recognition process. Our developed model may serve as a query tool for future virtual screening and drug designing for this particular target.