Bakherad Zohreh, Safavi Maliheh, Fassihi Afshin, Sadeghi-Aliabadi Hojjat, Bakherad Mohammad, Rastegar Hossein, Saeedi Mina, Ghasemi Jahan B, Saghaie Lotfollah, Mahdavi Mohammad
Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, 81746-73461, Isfahan, Iran.
Department of Biotechnology, Iranian Research Organization for Science and Technology, 33535-111, Tehran, Iran.
Chem Biodivers. 2019 Apr;16(4):e1800470. doi: 10.1002/cbdv.201800470. Epub 2019 Apr 3.
In this work, two novel series of indole-thiosemicarbazone derivatives were designed, synthesized, and evaluated for their cytotoxic activity against MCF-7, A-549, and Hep-G2 cell lines in comparison to etoposide and colchicine as the reference drugs. Generally, the synthesized compounds showed better cytotoxicity towards A-549 and Hep-G2 than MCF-7. Among them, (2E)-2-{[2-(4-chlorophenyl)-1H-indol-3-yl]methylidene}-N-(4-methoxyphenyl)hydrazinecarbothioamide (8l) was found to be the most potent compound against A-549 and Hep-G2, at least three times more potent than etoposide. The morphological analysis by the acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that compound 8l induced apoptosis in A-549 cells. Moreover, molecular docking methodology was exploited to elucidate the details of molecular interactions of the studied compounds with putative targets.
在本研究中，设计、合成了两个新型吲哚-硫代半卡巴腙衍生物系列，并与作为参比药物的依托泊苷和秋水仙碱相比，评估了它们对MCF-7、A-549和Hep-G2细胞系的细胞毒性活性。总体而言，合成的化合物对A-549和Hep-G2的细胞毒性比MCF-7更好。其中，(2E)-2-{[2-(4-氯苯基)-1H-吲哚-3-基]亚甲基}-N-(4-甲氧基苯基)肼基甲硫酰胺(8l)被发现是对A-549和Hep-G2最具活性的化合物，其活性至少比依托泊苷高三倍。通过吖啶橙/溴化乙锭双重染色试验进行的形态学分析和流式细胞术分析表明，化合物8l诱导A-549细胞凋亡。此外，利用分子对接方法阐明了所研究化合物与假定靶点的分子相互作用细节。
