QSAR Modeling on Benzo[c]phenanthridine Analogues as Topoisomerase I Inhibitors and Anti-cancer Agents

Molecules

Khac-Minh Thai¹  Quang-Huynh Bui¹  Thanh-Dao Tran¹ 

[1] 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

关键词: QSAR;    topoisomerase;    benzo[c]phenanthridine;    cytotoxicity;    model assessment;    confidence level;   

DOI  :  10.3390/molecules17055690

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.