title: Syntheses, cytotoxic activity evaluation and HQSAR study of 1,2,3-triazole-linked isosteviol derivatives as potential anticancer agents.
abstract: A series of novel 1,2,3-triazole-linked isosteviol derivatives were designed and synthesized via Huisgen-click reaction. Their cytotoxicities in vitro against HCT-116 and JEKO-1 cells were screened. The preliminary bioassays indicated that most of the title compounds exhibited noteworthy cytotoxic activities. Particularly, the compound 10b revealed the most potent inhibitory activities against HCT-116 cells with IC50value of 2.987±0.098μM, which was better than that (3.906±0.261μM) of positive control cisplatin. On the basis of these bioactivity data, hologram quantitative structure-activity relationship (HQSAR) was performed, and a statistically reliable model with good predictive power (r2=0.848, q2=0.544 and R2pred=0.982) was achieved. Additionally, the contribution maps derived from the optimal model explained the individual atomic contributions to the activity for each molecule.
authors: College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, 75 Daxue Road, Zhengzhou, Henan 450052, China; College of Chemical Engineering and Food Technology, Zhongzhou University, Zhengzhou, Henan 450044, China.
authors: Cong-Jun
authors: CJ
authors: Liu
authors: College of Chemical Engineering and Food Technology, Zhongzhou University, Zhengzhou, Henan 450044, China.
authors: Yan-Ping
authors: YP
authors: Liu
authors: Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, Henan University, Kaifeng, Henan 475004, China.
authors: Shu-Ling
authors: SL
authors: Yu
authors: College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, 75 Daxue Road, Zhengzhou, Henan 450052, China.
authors: Xing-Jie
authors: XJ
authors: Dai
authors: College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, 75 Daxue Road, Zhengzhou, Henan 450052, China.
authors: Tao
authors: T
authors: Zhang
authors: College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, 75 Daxue Road, Zhengzhou, Henan 450052, China. Electronic address: jctao@zzu.edu.cn.
authors: Jing-Chao
authors: JC
authors: Tao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D045786:Diterpenes, Kaurane / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D021281:Quantitative Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; D014230:Triazoles; C515747:isosteviol
keywords: Click chemistry; Cytotoxicity; HQSAR; Isosteviol; Synthesis