药学学报, 2019, 54(3): 514-521
引用本文:
马俊杰, 倪欣, 黄坤, 王瑜. 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[J]. 药学学报, 2019, 54(3): 514-521.
MA Jun-jie, NI Xin, HUANG Kun, WANG Yu. Design, synthesis and of antitumor activity study of coumarin derivatives bearing benzothiazole or benzene moiety[J]. Acta Pharmaceutica Sinica, 2019, 54(3): 514-521.

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
马俊杰, 倪欣, 黄坤, 王瑜
华侨大学医学院, 福建 泉州 362000
摘要:
本文基于procaspase-3激活剂1541系列的香豆素骨架结构,结合前期研究基础,设计合成了12个含苯并噻唑/苯基片段的香豆素衍生物,其结构经1H NMR、13C NMR和ESI-MS/HR-MS确证,以procaspase-3高表达的人组织细胞淋巴瘤细胞株(U937)和procaspase-3低表达的人乳腺癌细胞株(MCF-7)为测试细胞株,采用CCK-8法对目标化合物进行了体外抗肿瘤活性测试,初步验证目标化合物的靶向性,排除脱靶效应。结果表明,所设计的含苯并噻唑片段的香豆素衍生物对procaspase-3高表达的U937表现出较好的抑制作用和选择性,而对procaspase-3低表达的MCF-7无明显抑制作用。Caspase-3激活活性测试进一步表明,含苯并噻唑片段的香豆素衍生物表现出显著的caspase-3激活活性,其中化合物5f活性最强,激活率为93%。流式细胞术进一步验证了化合物5f能通过诱导细胞凋亡的方式抑制肿瘤细胞增殖。体外procaspase-3酶活性实验表明,化合物5f表现出较强的procaspase-3激活作用。
关键词:   
Design, synthesis and of antitumor activity study of coumarin derivatives bearing benzothiazole or benzene moiety
MA Jun-jie, NI Xin, HUANG Kun, WANG Yu
School of Medicine, Huaqiao University, Quanzhou 362000, China
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.
Key words:   
收稿日期: 2018-12-14
DOI: 10.16438/j.0513-4870.2018-1117
基金项目: 国家自然科学基金资助项目(81602970);福建省自然科学基金面上项目(2017J01143);2018年泉州高层次人次创新创业项目(2018C074R).
通讯作者: 马俊杰
Email: majunjie3612@hqu.edu.cn
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