Design, synthesis and of antitumor activity study of coumarinderivatives bearing benzothiazole or benzene moiety
10.16438/j.0513-4870.2018-1117
- VernacularTitle:含苯并噻唑/苯基片段的香豆素衍生物的设计、合成及抗肿瘤活性研究
- Author:
Jun-jie MA
1
;
Xin NI
1
;
Kun HUANG
1
;
Yu WANG
1
Author Information
1. School of Medicine, Huaqiao University, Quanzhou 362000, China
- Publication Type:Research Article
- Keywords:
benzothiazole;
coumarin;
esign;
synthesis;
antitumor activity
- From:
Acta Pharmaceutica Sinica
2019;54(3):514-521
- CountryChina
- Language:Chinese
-
Abstract:
Based on coumarin core structure as the procaspase-3 activator 1541 from our previous study, twelve coumarin derivatives bearing benzothiazole or benzene moiety were designed and synthesized. Target compounds were evaluated for in vitro antitumor activity against a procaspase-3 overexpressing cancer cell line (human histiocytic lymphoma cell, U937) and a procaspase-3 no-expression cancer cell line (human breast adenocarcinoma cell, MCF-7) to rule out off-target effects. The results revealed that coumarin derivatives bearing benzothiazole showed more potent inhibition activity and selectivity against procaspase-3 over-expressing cancer cell line (U937) than procaspase-3 low-sensitive cancer cell line (MCF-7). Caspase-3 activity evaluation showed that coumarin derivatives bearing benzothiazole showed remarkable caspase-3 activation activity, among them, compound 5f displayed the strongest activity with 93% degree. Flow cytometric assay revealed that compound 5f could inhibit proliferation of tumor cells by inducing apoptosis. Procaspase-3 activity assay showed that compound 5f showed strong procaspase-3 activation activity.
