title: Pharmacophore, QSAR, and ADME based semisynthesis and in vitro evaluation of ursolic acid analogs for anticancer activity.
abstract: In the present work, QSAR models for predicting the activities of ursolic acid analogs against human lung (A-549) and CNS (SF-295) cancer cell lines were developed by a forward stepwise multiple linear regression method using a leave-one-out approach. The regression coefficient (r(2)) and the cross-validation regression coefficient (rCV(2)) of the QSAR model for cytotoxic activity against the human lung cancer cell line (A-549) were 0.85 and 0.80, respectively. The QSAR study indicated that the LUMO energy, ring count, and solvent-accessible surface area were strongly correlated with anticancer activity. Similarly, the QSAR model for cytotoxic activity against the human CNS cancer cell line (SF-295) also showed a high correlation (r(2) = 0.99 and rCV(2) = 0.96), and indicated that dipole vector and solvent-accessible surface area were strongly correlated with activity. Ursolic acid analogs that were predicted to be active against these cancer cell lines by the QSAR models were semisynthesized and characterized on the basis of their (1)H and (13)C NMR spectroscopic data, and were then tested in vitro against the human lung (A-549) and CNS (SF-295) cancer cell lines. The experimental results obtained agreed well with the predicted values.
authors.affiliation: Analytical Chemistry Department, Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015 UP, India.
authors.forename: Komal
authors.initials: K
authors.lastname: Kalani
authors.forename: Dharmendra Kumar
authors.initials: DK
authors.lastname: Yadav
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Srivastava
authors.forename: Nitasha
authors.initials: N
authors.lastname: Suri
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D003198:Computer Simulation; D006801:Humans; D020128:Inhibitory Concentration 50; D008962:Models, Theoretical; D056004:Molecular Dynamics Simulation; D021281:Quantitative Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; D000097245:Ursolic Acid