Title

Molecular docking studies on quinazoline antifolate derivatives as human thymidylate synthase inhibitors

Authors

V. Srivastava^1,4, S.P.Gupta², M. I. Siddiqi ³, B.N. Mishra^4*

Affiliation

¹ Department of Biotechnology, Meerut Institute of Engineering & Technology, Meerut-250005; ² Department of Pharmacy, Meerut Institute of Engineering & Technology, Meerut-250005; ³Computational Biology and Bioinformatics Lab., MSB Division, Central Drug Research Institute, Lucknow- 226001; ⁴Department of Biotechnology, Institute of Engineering & Technology, UP Technical University Campus, Sitapur Road, Lucknow- 226021

Email

profbnmishra@gmail.com

Article Type

Hypothesis

Date

Received October 30, 2009; Accepted November 15, 2009; Published February 28, 2010

Abstract

We have performed molecular docking on quinazoline antifolates complexed with human thymidylate synthase to gain insight into the structural preferences of these inhibitors. The study was conducted on a selected set of one hundred six compounds with variation in structure and activity. The structural analyses indicate that the coordinate bond interactions, the hydrogen bond interactions, the van der Waals interactions as well as the hydrophobic interactions between ligand and receptor are responsible simultaneously for the preference of inhibition and potency. In this study, fast flexible docking simulations were performed on quinazoline antifolates derivatives as human thymidylate synthase inhibitors. The results indicated that the quinazoline ring of the inhibitors forms hydrophobic contacts with Leu192, Leu221 and Tyr258 and stacking interaction is conserved in complex with the inhibitor and cofactor.

Keywords

Human thymidylate synthase, Quinazoline antifolate derivatives and Molecular docking.

Citation

Srivastava et al., Bioinformation, 4(8): 357-365 (2010)

Edited by

P. Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.