Journal of Chemistry

Journal of Chemistry / 2012 / Article

Open Access

Volume 9 |Article ID 201937 | 12 pages | https://doi.org/10.1155/2012/201937

3D QSAR of Pyrrolo Pyrimidine and Thieno Pyrimidines as Human Thymidylate Synthase Inhibitors

Received08 Sep 2011
Accepted11 Nov 2011

Abstract

Thymidylate synthase (TS) is a crucial enzyme for DNA biosynthesis and many nonclassical lipophilic antifolates targeting this enzyme are quite efficient and encouraging as antitumor drugs. We report 3D-QSAR analyses on pyrrolo pyrimidine and thieno pyrimidine antifolates to contemplate the mechanism of action and structure-activity relationship of these molecules. By applying leave-one-out (LOO) cross-validation study, cross-validated q2 value of 0.523 and 0.566 for CoMFA Ligand based (LB) and Receptor based (RB), 0.516 and 0.471 for CoMSIA LB and RB respectively. while the non-cross-validated r2 values were found to be 0.974 and 0.969 for CoMFA LB and RB, 0.983 and 0.972 for CoMSIA LB and RB respectively. The models were graphically interpreted using CoMFA and CoMSIA contour plots. The results obtained from this study were used for rational design of potent inhibitors against thymidylate synthase.

Copyright © 2012 Hindawi Publishing Corporation. 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.


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