Mahdavi Mohammad, Pedrood Keyvan, Safavi Maliheh, Saeedi Mina, Pordeli Mahboobeh, Ardestani Sussan Kabudanian, Emami Saeed, Adib Mehdi, Foroumadi Alireza, Shafiee Abbas
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran.
Eur J Med Chem. 2015 May 5;95:492-9. doi: 10.1016/j.ejmech.2015.03.057. Epub 2015 Mar 26.
A novel series of 2-arylquinazolinones 7a-o bearing trans-stilbene moiety were designed, synthesized, and evaluated against human breast cancer cell lines including human breast adenocarcinoma (MCF-7 and MDA-MB-231) and human ductal breast epithelial tumor (T-47D). Among the tested compounds, the sec-butyl derivative 7h showed the best profile of activity (IC50 < 5 μM) against all cell lines, being 2-fold more potent than standard drug, etoposide. Our investigation revealed that the cytotoxic activity was significantly affected by N3-alkyl substituents. Furthermore, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that the prototype compound 7h can induce apoptosis in MCF-7 and MDA-MB-231 cells.
设计、合成了一系列新型的带有反式芪基部分的2-芳基喹唑啉酮7a-o，并针对包括人乳腺腺癌（MCF-7和MDA-MB-231）以及人乳腺导管上皮肿瘤（T-47D）在内的人乳腺癌细胞系进行了评估。在测试的化合物中，仲丁基衍生物7h对所有细胞系均表现出最佳活性（IC50 < 5 μM），其效力比标准药物依托泊苷高2倍。我们的研究表明，N3-烷基取代基对细胞毒性活性有显著影响。此外，通过吖啶橙/溴化乙锭双重染色试验和流式细胞术分析进行的形态学分析表明，原型化合物7h可诱导MCF-7和MDA-MB-231细胞凋亡。
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