1. Syntheses, cytotoxic activity evaluation and HQSAR study of 1,2,3-triazole-linked isosteviol derivatives as potential anticancer agents
- Author
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Yan-Ping Liu, Jing-Chao Tao, Cong-Jun Liu, Tao Zhang, Xing-Jie Dai, and Shu-Ling Yu
- Subjects
Models, Molecular ,1,2,3-Triazole ,Cell Survival ,Stereochemistry ,Clinical Biochemistry ,Quantitative Structure-Activity Relationship ,Pharmaceutical Science ,Positive control ,Antineoplastic Agents ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Neoplasms ,Drug Discovery ,Humans ,Cytotoxic T cell ,Cytotoxicity ,Molecular Biology ,IC50 ,010405 organic chemistry ,Organic Chemistry ,Triazoles ,HCT116 Cells ,Combinatorial chemistry ,In vitro ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry ,Click chemistry ,Molecular Medicine ,Click Chemistry ,Drug Screening Assays, Antitumor ,Diterpenes, Kaurane - 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 IC50 value 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.
- Published
- 2016