In vitro cytotoxicity of novel 2,5,7-tricarbo-substituted indoles derived from 2-amino-5-bromo-3-iodoacetophenone

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• 作者：Malose J. Mphahlele^a ; ^{mphahmj@unisa.ac.za" class="auth_mail" title="E-mail the corresponding author} ; Tshepiso J. Makhafola^b ; Mmakwena M. Mmonwa^a
• 关键词：2-Amino-5-bromo-3-iodoacetophenone ; Cross-coupling ; Heteroannulation ; Polycarbo-substituted indoles ; Cytotoxicity ; Apoptosis
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 October 2016
• 年：2016
• 卷：24
• 期：19
• 页码：4576-4586
• 全文大小：1301 K

文摘

A series of novel 2,5,7-tricarbo-substituted indoles were prepared via sequential Sonogashira and Suzuki–Miyaura cross-coupling of 2-amino-5-bromo-3-iodoacetophenone with terminal acetylenes and aryl/styrylboronic acids followed by palladium chloride-mediated heteroannulation of the incipient 5-aryl/styryl-substituted 2-amino-3-(arylalkynyl)acetophenones. These polycarbo-substituted indole derivatives were evaluated for potential in vitro antiproliferative activity against the human breast adenocarcinoma (MCF-7) and human cervical cancer (HeLa) cell lines. Compounds 6f, 6i, 6k, 6m and 6n were found to exhibit significant cytotoxicity and selectivity against the HeLa cells. Compounds 6i and 6m were chosen as representative examples to evaluate their pro-apoptotic efficacy against the HeLa cell line. The compounds induced apoptosis through cell membrane alteration and DNA fragmentation caspase-dependent pathways.