Affiliation:
1. Department of Atomic and Molecular Physics, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal-576104, India
2. Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal-576104, India
Abstract
Apoptosis is a vital physiological process, which is observed in various biological events. The
anti-apoptotic and pro-apoptotic members of Bcl-2 family are the most characterized proteins which are
involved in the regulation of apoptotic cell death. The anti-apoptotic proteins such as Bcl-2 and Bcl-xL
prevent apoptosis, whereas pro-apoptotic members like Bax and Bak, elicit the release of caspases from
death antagonists inducing apoptosis. Thus, the Bcl-2 family of proteins play a vital role in controlling
programmed cell death. Over expression of anti-apoptotic Bcl-2 proteins are often directly associated
with various kinds of cancer. Developing suitable inhibitors for controlling the elevated levels of these
proteins got much attention in last decade. Structural biology techniques such as Nuclear Magnetic
Resonance (NMR) spectroscopy, X-ray crystallography, homology modeling and molecular docking
play a significant role in identifying the key inhibitors of these proteins. The authors have developed and
tested successfully, several series of indole pharmacore containing inhibitors for Bcl-2 and Bcl-xL proteins
based on the homology modeling, docking and suitable biochemical and apoptosis assays. This
review provides a summary of potential inhibitor molecules developed for Bcl-2 and Bcl-xL proteins, as
well as the the key residues of these proteins interacting with potential drug molecules. The present appraisal
also focuses on the role of computational algorithms in developing potential drug molecules,with
more emphasis on the role of homology modeling and docking studies in developing inhibitors for Bcl-
2, and Bcl-xL proteins in cancer therapy.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,General Medicine
Cited by
23 articles.
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