QSAR Guided Semi-synthesis and In-Vitro Validation of Anticancer Activity in Ursolic Acid Derivatives

ISSN: 1873-5294 (Online)
ISSN: 1568-0266 (Print)


Volume 14, 24 Issues, 2014


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Current Topics in Medicinal Chemistry

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  • 9th of 59 in Chemistry, Medicinal



Editor-in-Chief:
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Fox Chase Chemical Diversity Center, Inc
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QSAR Guided Semi-synthesis and In-Vitro Validation of Anticancer Activity in Ursolic Acid Derivatives

Author(s): Komal Kalani, Dharmendra K. Yadav, Aru Singh, Feroz Khan, M.M. Godbole and S.K. Srivastava

Affiliation: Medicinal Chemistry Department, CSIR-CIMAP, Lucknow-226015 (U.P), India.

Abstract

As a part of our anticancer drug discovery programme, QSAR models were developed for the prediction of anticancer activities of ursolic acid derivatives against the human hepatocellular carcinoma HepG2, breast carcinoma MDA-MB-231 and the human ductal breast epithelial T47D cancer cell lines followed by wet lab semi-synthesis of virtually active derivatives, their in-vitro biological evaluation and apoptosis. The development of QSAR models was carried out by forward stepwise multiple linear regression method using a leave-one-out approach. Virtually active derivatives were semi synthesized, spectroscopically characterized and then in-vitro tested against human cancer cell lines. Active derivatives were checked via DNA fragmentation assay. The results exhibited regression coefficients (r2) and the cross-validation regression coefficients (rCV2) for the human HepG2, MDA-MB-231 and T47D cancer cell lines as .95 and .90; .92 and .87; .89 and .83 respectively showing the prediction accuracy of the models against biological activities. Computational molecular modeling is a valid modern approach, widely used in the identification of potential drug leads. The most active virtual derivatives of UA were semi- synthesized and their in-vitro and ex-vivo evaluation showed similar results with the predicted one, validating our QSAR models. Out of several active derivatives, the three UA2, UA7 and UA10 were potentially active against the above human cancer cell lines. These findings may be of immense importance in the anticancer drug development of an inexpensive and widely available natural product, ursolic acid.




Keywords: QSAR modeling, ursolic acid derivatives, in-vitro anticancer activity, apoptosis assay.

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Article Details

Volume: 14
Issue Number: 8
First Page: 1005
Last Page: 1013
Page Count: 9
DOI: 10.2174/1568026614666140324121606
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