Microwave‐Assisted Syntheses of Benzimidazole‐Containing Selenadiazole Derivatives That Induce Cell‐Cycle Arrest and Apoptosis in Human Breast Cancer Cells by Activation of the ROS/AKT Pathway. (28th September 2016)

• Record Type: Journal Article
• Authors: Liang, Yuanwei; Zhou, Yangliang; Deng, Shulin; Chen, Tianfeng
• Is Part Of: ChemMedChem. Volume 11:Number 20(2016)
• Page Start: 2339
• Page End: 2346
• Publication Date: 2016-09-28
• Subjects: apoptosis -- benzimidazoles -- microwave irradiation -- reactive oxygen species -- selenadiazoles; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600261
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: The use of selenium‐containing heterocyclic compounds as potent cancer chemopreventive and chemotherapeutic agents has been well documented by a large number of clinical studies. In this study we developed a new approach to synthesize four benzimidazole‐containing selenadiazole derivatives (BSeDs). The method uses a combination of peptide coupling reagents and microwave irradiation. This strategy features milder reaction conditions, higher yields, and shorter reaction times. The synthetic BSeDs were identified as potent antiproliferative agents against the human MCF‐7 and MDA‐MB‐231 breast cancer cell lines. Compounds1 b (5‐(6‐methyl‐1 H ‐benzo[ d ]imidazol‐2‐yl)benzo[ c ][1, 2, 5]selenadiazole), 1 c (5‐(6‐chloro‐1 H ‐benzo[ d ]imidazol‐2‐yl)benzo[ c ][1, 2, 5]selenadiazole), and1 d (5‐(6‐bromo‐1 H ‐benzo[ d ]imidazol‐2‐yl)benzo[ c ][1, 2, 5]selenadiazole) were found to show greater cytotoxicity against the triple‐negative breast cancer cell line MDA‐MB‐231 than MCF‐7, and to exhibit dose‐dependent inhibition of cell migration, in which a significant decrease in the zone of cell monolayer wound closure was observed relative to untreated controls. Our results demonstrate that BSeDs can cause cell‐cycle arrest and apoptosis in MDA‐MB‐231 cells by inducing DNA damage, inhibiting protein kinase B (AKT), and activating mitogen‐activated protein kinase (MAPK) family members through the overproduction of reactive oxygen species (ROS). Taken together, the results of this study provide a facile microwave‐assisted strategy for the synthesis of selenium‐containing organic compounds that exhibit a high level of anticancer efficacy. Abstract : Here′s a better way : We developed a new way to synthesize benzimidazole‐containing selenadiazole derivatives (BSeDs) by combining peptide coupling reagents and microwave irradiation. These derivatives were found to have high efficacy against the triple‐negative breast cancer cell line MDA‐MB‐231 and to exhibit dose‐dependent inhibition of cell migration. BSeDs cause MDA‐MB‐231 cell‐cycle arrest and apoptosis by inducing DNA damage, inactivating AKT, and activating MAPK family members by the overproduction of reactive oxygen species.