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QSAR Modeling on Benzo[c]phenanthridine Analogues as Topoisomerase I Inhibitors and Anti-cancer Agents
Department of Medicinal Chemistry, School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, 41 Dinh Tien Hoang St., Dist. 1, Ho Chi Minh City, Vietnam
* Author to whom correspondence should be addressed.
Received: 5 April 2012; in revised form: 25 April 2012 / Accepted: 4 May 2012 / Published: 11 May 2012
Abstract: Benzo[c]phenanthridine (BCP) derivatives were identified as topoisomerase I (TOP-I) targeting agents with pronounced antitumor activity. In this study, hologram-QSAR, 2D-QSAR and 3D-QSAR models were developed for BCPs on topoisomerase I inbibitory activity and cytotoxicity against seven tumor cell lines including RPMI8402, CPT-K5, P388, CPT45, KB3-1, KBV-1and KBH5.0. The hologram, 2D, and 3D-QSAR models were obtained with the square of correlation coefficient R2 = 0.58 − 0.77, the square of the crossvalidation coefficient q2 = 0.41 − 0.60 as well as the external set’s square of predictive correlation coefficient r2 = 0.51 − 0.80. Moreover, the assessment method based on reliability test with confidence level of 95% was used to validate the predictive power of QSAR models and to prevent over-fitting phenomenon of classical QSAR models. Our QSAR model could be applied to design new analogues of BCPs with higher antitumor and topoisomerase I inhibitory activity.
Keywords: QSAR; topoisomerase; benzo[c]phenanthridine; cytotoxicity; model assessment; confidence level
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Thai, K.-M.; Bui, Q.-H.; Tran, T.-D.; Huynh, T.-N.-P. QSAR Modeling on Benzo[c]phenanthridine Analogues as Topoisomerase I Inhibitors and Anti-cancer Agents. Molecules 2012, 17, 5690-5712.
Thai K-M, Bui Q-H, Tran T-D, Huynh T-N-P. QSAR Modeling on Benzo[c]phenanthridine Analogues as Topoisomerase I Inhibitors and Anti-cancer Agents. Molecules. 2012; 17(5):5690-5712.
Thai, Khac-Minh; Bui, Quang-Huynh; Tran, Thanh-Dao; Huynh, Thi-Ngoc-Phuong. 2012. "QSAR Modeling on Benzo[c]phenanthridine Analogues as Topoisomerase I Inhibitors and Anti-cancer Agents." Molecules 17, no. 5: 5690-5712.