title: In vitro cytotoxicity of novel 2,5,7-tricarbo-substituted indoles derived from 2-amino-5-bromo-3-iodoacetophenone.
abstract: 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.
authors: Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa. Electronic address: mphahmj@unisa.ac.za.
authors: Malose J
authors: MJ
authors: Mphahlele
authors: Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa.
authors: Tshepiso J
authors: TJ
authors: Makhafola
authors: Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa.
authors: Mmakwena M
authors: MM
authors: Mmonwa
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000586:Amination; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D054879:Halogenation; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D061986:MCF-7 Cells; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
chemical_list: D000098:Acetophenones; D000970:Antineoplastic Agents; D007211:Indoles; C038699:acetophenone
keywords: 2-Amino-5-bromo-3-iodoacetophenone; Apoptosis; Cross-coupling; Cytotoxicity; Heteroannulation; Polycarbo-substituted indoles