Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 45, Issue 4, Pages 1560-1571Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2009.12.065
Keywords
CoMFA; CoMSIA; QSAR; Quinazolines; Thymidylate synthase inhibitors
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Funding
- CSIR, New Delhi
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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. Herein, we report some 3D-QSAR analyses using CoMFA and CoMSIA on quinozoline antifolates in order to have a better understanding of the mechanism of action and structure-activity relationship of these compounds. By applying leave-one-out (LOO) cross-validation study, we obtained cross-validated q(2) value of 0.573 for CoMFA and 0.445 for CoMSIA, while the non-cross-validated r(2) values for them were found to be 0.935 and 0.893, respectively. The models were graphically interpreted using CoMFA and CoMSIA contour plots. The results obtained from this study could be used for rational design of potent inhibitors against thymidylate synthase. (c) 2010 Elsevier Masson SAS. All rights reserved.
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