title: Synthesis, cytotoxic activity evaluation and HQSAR study of novel isosteviol derivatives as potential anticancer agents.
abstract: A series of novel isosteviol derivatives bearing amino alcohol and thiourea fragments have been stereo-selectively synthesized and screened for their in vitro cytotoxic activities against three human cancer cell lines (HCT-116, HGC-27 and JEKO-1). The results demonstrated that these compounds exhibited prominent cytotoxicities. Especially, the compound Iw displayed the most potent anticancer activities against HCT-116 cell with IC50 value of 1.450 μM. On the basis of this bioassay results, these derivatives were further investigated by the hologram quantitative structure-activity relationship (HQSAR) technique. The optimal HQSAR model with q(2) = 0.663, r(2) = 0.895, SEE = 0.179 was generated using A/B/H/Ch as fragment distinction parameters and 4-7 as fragment size. This model was employed to predict the cytotoxic activities of test set compounds, and the predicted values were in good agreement with the experimental results. The contribution maps derived from the optimal model explained the individual atomic contribution to the total activity of single molecule.
authors.affiliation: College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, 75 Daxue Road, Zhengzhou, Henan 450052, PR China; College of Chemical Engineering and Food Technology, Zhongzhou University, Zhengzhou, Henan 450044, PR China.
authors.forename: Cong-Jun
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, Henan University, Kaifeng, Henan 475004, PR China.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Yu
authors.affiliation: College of Chemical Engineering and Food Technology, Zhongzhou University, Zhengzhou, Henan 450044, PR China.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, 75 Daxue Road, Zhengzhou, Henan 450052, PR 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, 75 Daxue Road, Zhengzhou, Henan 450052, PR 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, 75 Daxue Road, Zhengzhou, Henan 450052, PR China. Electronic address: liruijun@zzu.edu.cn.
authors.forename: Rui-Jun
authors.initials: RJ
authors.lastname: Li
authors.affiliation: College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, 75 Daxue Road, Zhengzhou, Henan 450052, PR China. Electronic address: jctao@zzu.edu.cn.
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; D049109:Cell Proliferation / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D045786:Diterpenes, Kaurane; C515747:isosteviol
keywords: Anticancer activity; HQSAR; Isosteviol; Synthesis