Table of Contents
ISRN Medicinal Chemistry
Volume 2014, Article ID 203518, 14 pages
http://dx.doi.org/10.1155/2014/203518
Research Article

1,4-Dihydropyridine Calcium Channel Blockers: Homology Modeling of the Receptor and Assessment of Structure Activity Relationship

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt

Received 28 September 2013; Accepted 5 December 2013; Published 10 February 2014

Academic Editors: R. B. de Alencastro, P. L. Kotian, O. A. Santos-Filho, L. Soulère, and S. Srichairatanakool

Copyright © 2014 Moataz A. Shaldam 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.

Abstract

1,4-Dihydropyridine (DHP), an important class of calcium antagonist, inhibits the influx of extracellular Ca+2 through L-type voltage-dependent calcium channels. Three-dimensional (3D) structure of calcium channel as a receptor for 1,4-dihydropyridine is a step in understanding its mode of action. Protein structure prediction and modeling tools are becoming integral parts of the standard toolkit in biological and biomedical research. So, homology modeling (HM) of calcium channel alpha-1C subunit as DHP receptor model was achieved. The 3D structure of potassium channel was used as template for HM process. The resulted dihydropyridine receptor model was checked by different means to assure stereochemical quality and structural integrity of the model. This model was achieved in an attempt to understand the mode of action of DHP calcium channel antagonist and in further computer-aided drug design (CADD) analysis. Also the structure-activity relationship (SAR) of DHPs as antihypertensive and antianginal agents was reviewed, summarized, and discussed.