Syntheses, cytotoxic activity evaluation and HQSAR study of 1,2,3-triazole-linked isosteviol derivatives as potential anticancer agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 26; no. 22; pp. 5455 - 5461
• Main Authors: Liu, Cong-Jun, Liu, Yan-Ping, Yu, Shu-Ling, Dai, Xing-Jie, Zhang, Tao, Tao, Jing-Chao
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.11.2016; Elsevier
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Survival - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Click Chemistry; Cytotoxicity; Diterpenes, Kaurane - chemical synthesis; Diterpenes, Kaurane - chemistry; Diterpenes, Kaurane - pharmacology; Drug Screening Assays, Antitumor; HCT116 Cells; HQSAR; Humans; Isosteviol; Life Sciences & Biomedicine; Models, Molecular; Neoplasms - drug therapy; Pharmacology & Pharmacy; Physical Sciences; Quantitative Structure-Activity Relationship; Science & Technology; Synthesis; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology; Isosteviol; Cytotoxicity; Synthesis; Click chemistry; HQSAR; DESIGN; LEUCOVORIN; STEVIOL; ANALOGS; RATS; STEREOSELECTIVE-SYNTHESIS; FLUOROURACIL
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.10.028

[Display omitted] •A series of novel 1,2,3-triazole-linked isosteviol derivatives were synthesized.•Their cytotoxicities were assessed against HCT-116 and JEKO-1cell lines.•Compound 10b is promising anticancer agent against HCT-116 (IC50=2.987±0.098μM).•HQSAR studies revealed good predictive model. 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.