title: QSAR modeling on benzo[c]phenanthridine analogues as topoisomerase I inhibitors and anti-cancer agents.
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 = 0.5-0.80. 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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, University of Medicine and Pharmacy, 41 Dinh Tien Hoang St., Dist. 1, Ho Chi Minh City, Vietnam. thaikhacminh@uphcm.edu.vn
authors.forename: Khac-Minh
authors.initials: KM
authors.lastname: Thai
authors.forename: Quang-Huynh
authors.initials: QH
authors.lastname: Bui
authors.forename: Thanh-Dao
authors.initials: TD
authors.lastname: Tran
authors.forename: Thi-Ngoc-Phuong
authors.initials: TN
authors.lastname: Huynh
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D010617:Phenanthridines / Q000138:chemical synthesis* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D010617:Phenanthridines; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human