Chinese Journal of Organic Chemistry >
Design and Synthesis of Novel Nature-Inspired Stilbene Analogues as Potential Topoisomerase 1 Inhibitors
Received date: 2021-02-19
Revised date: 2021-04-16
Online published: 2021-05-14
Supported by
Natural Science Foundation of Zhejiang Province(LY17C140003)
In order to find novel antitumor drug leads, twenty-three nature-inspired stilbene analogues containing thiazole moiety were designed and synthesized, and their structures were confirmed by NMR and ESI-HRMS. These compounds were screened for their topoisomerase I (Top1) inhibitory activity using Top1-mediated relaxation assay, and (E)-5-bromo-2- (2-chlorostyryl)-4-(4-fluorophenyl)thiazole (6k) possessed promising Top1 inhibitory activity. Molecular docking was also established to study the structure-activity relationship and a good correlation was observed between Top1 inhibitory activity and molecular docking study. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against human breast cancer (MCF-7) and human colon cancer (HCT116) cell lines indicated that (E)-5-bromo-4-(4-fluorophenyl)- 2-(4-(trifluoromethyl)styryl)thiazole (6e), (E)-5-bromo-2-(2-chlorostyryl)-4-(4-fluorophenyl)thiazole (6k), and (E)-5-bromo- 2-(4-chlorostyryl)-4-(4-fluorophenyl)thiazole (6l) showed high cytotoxicity at low micromolar concentrations.
Key words： natural stilbene; thiazole; topoisomerase 1 inhibitor; synthesis; cytotoxicity
Qi Lu , Feixia Ye , Xiaotong Sun , Jianquan Weng , Qian Yu , Dexuan Hu . Design and Synthesis of Novel Nature-Inspired Stilbene Analogues as Potential Topoisomerase 1 Inhibitors[J]. Chinese Journal of Organic Chemistry, 2021 , 41(8) : 3321 -3329 . DOI: 10.6023/cjoc202102031
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