662150-78-9Relevant articles and documents
Trisubstituted-imidazoles induce apoptosis in human breast cancer cells by targeting the oncogenic PI3K/Akt/mTOR signaling pathway
Mohan, Chakrabhavi Dhananjaya,Srinivasa,Rangappa, Shobith,Mervin, Lewis,Mohan, Surender,Paricharak, Shardul,Baday, Sefer,Li, Feng,Shanmugam, Muthu K.,Chinnathambi, Arunachalam,Zayed,Alharbi, Sulaiman Ali,Bender, Andreas,Sethi, Gautam,Basappa,Rangappa, Kanchugarakoppal S.
, (2016/07/18)
Overactivation of PI3K/Akt/mTOR is linked with carcinogenesis and serves a potential molecular therapeutic target in treatment of various cancers. Herein, we report the synthesis of trisubstituted-imidazoles and identified 2-chloro-3-(4, 5-diphenyl-1H-imidazol-2-yl) pyridine (CIP) as lead cytotoxic agent. Na?ve Base classifier model of in silico target prediction revealed that CIP targets RAC-beta serine/threonine-protein kinase which comprises the Akt. Furthermore, CIP downregulated the phosphorylation of Akt, PDK and mTOR proteins and decreased expression of cyclin D1, Bcl-2, survivin, VEGF, procaspase-3 and increased cleavage of PARP. In addition, CIP significantly downregulated the CXCL12 induced motility of breast cancer cells and molecular docking calculations revealed that all compounds bind to Akt2 kinase with high docking scores compared to the library of previously reported Akt2 inhibitors. In summary, we report the synthesis and biological evaluation of imidazoles that induce apoptosis in breast cancer cells by negatively regulating PI3K/Akt/mTOR signaling pathway. Copyright:
ARYL IMIDAZOLES AND THEIR USE AS ANTI-CANCER AGENTS
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Page/Page column 78-79, (2008/06/13)
Therapeutically effective 2,4,5-trisubstituted imidazole compounds are provided. Also provided are methods -of preparing the compounds and pharmaceutical compositions comprising the compounds alone or in combination with other agents. The present inventio
