title: Synthesis, cytotoxic activity, and 2D- and 3D-QSAR studies of 19-carboxyl-modified novel isosteviol derivatives as potential anticancer agents.
abstract: Two series of novel acylthiosemicarbazide and oxadiazole fused-isosteviol derivatives were synthesized based on the 19-carboxyl modification. The target compounds were evaluated for their cytotoxicities against three cancer cell lines (HCT-116, HGC-27, and JEKO-1) using an MTT assay. Lead compounds from the acylthiosemicarbazides (4) showed IC50values in the lower micromolar range. For example, compounds (4i, 4l, 4m, 4r, and 4s) exhibited significant inhibitory activities against the three cell lines with IC50values of 0.95-3.36 μm. Furthermore, 2D-HQSAR and 3D-topomer CoMFA analyses were established, which could be used to develop second generation of isosteviol derivatives as anticancer agents.
authors.affiliation: College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Cong-Jun
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, Henan University, Kaifeng, Henan, China.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Yu
authors.affiliation: College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Dai
authors.affiliation: College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Jing-Chao
authors.initials: JC
authors.lastname: Tao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D045786:Diterpenes, Kaurane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; D010069:Oxadiazoles; D012663:Semicarbazides; C515747:isosteviol; C005151:thiosemicarbazide
keywords: 2D-HQSAR; 3D-topomer CoMFA; cytotoxicity; isosteviol derivatives; synthesis