Title: Computer-aided virtual screening of Telmisartan analogues as possible CDK cell cycle inhibitors
Authors: Satyanarayana Kotha; Yesu Babu Adimulam; Kiran Kumar Reddi
Addresses: Department of Information Technology, Sir C.R. Reddy College of Engineering, Eluru 534007, India ' Department of Computer Science and Engineering, Sir C.R. Reddy College of Engineering, Eluru 534007, India ' Department of Computer Science, Krishna University, Machilipatnam 521001, India
Abstract: Cyclin dependent kinases (CDKs) act as potential therapeutic targets in cancer disease and automated docking was performed on a set of 144 Telmisartan analogues containing imidazole rings which are reported as angiotensin II receptor antagonists. Molecular docking analysis of CDKs 2, 4 and 5 resulted in better binding affinities within the active site region of each CDK. Compounds 122 and 121 are selective towards CDK2 and CDK4 inhibitions, whereas compounds 131, 133 and 134 were found to be selective towards CDK4 and CDK5 inhibitions. Compound 27 was found to be highly selective towards CDK2 with binding affinity of −201.547 kcal/mol when compared with dock scores of CDK4 and CDK5 (−195.687 and −170.421 kcal/mol). On the basis of geometric orientation of docked poses within active sites of CDKs, it was observed that the presence of triazole and tetrazole groups on these compounds is responsible for better inhibitory activities.
Keywords: CDK inhibition; molecular docking; triazole; tetrazole; computer-aided screening; virtual screening; Telmisartan analogues; CDK cell cycle inhibitors; cyclin dependent kinases; therapeutic targets; cancer; imidazole rings.
International Journal of Computational Biology and Drug Design, 2015 Vol.8 No.4, pp.359 - 382
Received: 07 May 2015
Accepted: 25 Jul 2015
Published online: 15 Dec 2015 *