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E-Journal of Chemistry
Volume 9 (2012), Issue 4, Pages 1699-1710

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

Molecular Modelling and Medicinal Chemistry Group, Department of Chemistry, Nizam College, Osmania University, Hyderabad-500 001, India

Received 8 September 2011; Accepted 11 November 2011

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.


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.