Syntheses, cytotoxic activity evaluation and HQSAR study of 1,2,3-triazole-linked isosteviol derivatives as potential anticancer agents
- Bioorg Med Chem Lett. 2016 Nov 15;26(22):5455-5461. doi: 10.1016/j.bmcl.2016.10.028.
- 1. 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.
- 2. College of Chemical Engineering and Food Technology, Zhongzhou University, Zhengzhou, Henan 450044, China.
- 3. Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, Henan University, Kaifeng, Henan 475004, China.
- 4. College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, 75 Daxue Road, Zhengzhou, Henan 450052, China.
- 5. College of Chemistry and Molecular Engineering, New Drug Research & Development Center, Zhengzhou University, 75 Daxue Road, Zhengzhou, Henan 450052, China. Electronic address: [email protected].
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.