4-氧代-2-亚胺基噻唑烷-5-亚基乙酸乙酯类化合物的设计、合成及抗癌活性
收稿日期: 2022-10-21
修回日期: 2022-11-23
网络出版日期: 2022-12-14
基金资助
国家自然科学基金(22167002); 国家自然科学基金(21867001); 江西省教育厅(GJJ201429); 赣南师范大学研究生创新(YCX21A027)
Design, Synthesis and in vitro Anti-Cancer Activity of Novel Ethyl 4-Oxo-2-iminothiazolidin-5-ylidene Acetates
Received date: 2022-10-21
Revised date: 2022-11-23
Online published: 2022-12-14
Supported by
National Natural Science Foundation of China(22167002); National Natural Science Foundation of China(21867001); Education Department of Jiangxi Province(GJJ201429); Graduate Innovation Research Project of Gannan Normal University(YCX21A027)
以胺、异硫氰酸酯和炔酯为原料, 通过三组分偶联环化制备了一系列4-氧代-2-亚胺基噻唑烷-5-亚基乙酸乙酯类化合物. 采用噻唑蓝(MTT)法研究了目标化合物对人肝癌细胞HepG2和人乳腺癌细胞MCF-7的体外抗癌活性, 结果发现大多数化合物显示出明显的抗癌活性. 与顺铂相比, (Z)-2-((Z)-2-((3,4-二氯苯基)亚氨基)-3-(3-(4-甲基哌嗪-1-基)丙基)-4-氧代噻唑烷-5-亚基)乙酸乙酯(4r)表现出最好的细胞毒性, 对HepG2和MCF-7的IC50值分别为0.88和0.80 μmol/L, 并且讨论了药物的初步构效关系. 这些化合物对肿瘤细胞具有良好的生物活性, 是一类有应用前景的化学治疗药物, 值得进行后续研究.
关键词： 4-氧代-2-亚胺基噻唑烷-5-亚基乙酸乙酯; 抗癌活性; 基于结构的药物设计; 构效关系
钟玉梅 , 邹小颖 , 卓小丫 , 王逸涵 , 申佳奕 , 郑绿茵 , 郭维 . 4-氧代-2-亚胺基噻唑烷-5-亚基乙酸乙酯类化合物的设计、合成及抗癌活性[J]. 有机化学, 2023 , 43(4) : 1452 -1461 . DOI: 10.6023/cjoc202210023
A series of novel ethyl 4-oxo-2-iminothiazolidin-5-ylidene acetate derivatives were synthesized through the three- component coupling annulation of amines, isothiocyanates and diethyl but-2-ynedioates. The obtained compounds were assayed in vitro for their anti-cancer activities against human liver cancer (HepG2) and human breast cancer (MCF-7) cell lines by standard methyl thiazolyl tetrazolium (MTT) method, most of which exhibited significant cytotoxicity. In particular, ethyl (Z)-2-((Z)-2-((3,4-dichlorophenyl)imino)-3-(3-(4-methylpiperazin-1-yl)propyl)-4-oxothiazolidin-5-ylidene)-acetate (4r) displayed the highest level of cytotoxicity compared with cisplatin, and its IC50 values for HepG2 and MCF-7 cells were 0.88 and 0.80 μmol/L, respectively. Their preliminary structure-activity relationship was also discussed. The remarkable cytotoxic nature of these substances against cancer cells could be considered as promising chemotherapeutic agents to be developed in future.
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