Trisubstituted-imidazoles induce apoptosis in human breast cancer cells by targeting the oncogenic PI3K/Akt/mTOR signaling pathway

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Chakrabhavi, Dhananjaya Mohan. and Srinivasa, V. and Shobith, Rangappa. and Lewis, Mervin. and Surender, Mohan. and Shardul, Paricharak. and Sefer, Baday. and Feng, Li. and Muthu, K.Shanmugam. and Arunachalam, Chinnathambi. and Zayed, M.E. and Sulaiman Ali, Alharbi. and Andreas, Bender. and Gautam, Sethi. and Basappa, . and Kanchugarakoppal, S.Rangappa. (2016) Trisubstituted-imidazoles induce apoptosis in human breast cancer cells by targeting the oncogenic PI3K/Akt/mTOR signaling pathway. Neuroscience 2016. pp. 1-15.

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Official URL: https://doi.org/10.1371/journal.pone.0153155

Abstract

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. Naïve 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.

Item Type: Article
Subjects: Faculty of Science > Pure Sciences > Chemistry
Divisions: Jnana Bharathi / Central College Campus > Department of Chemistry
Depositing User: Mr. Prashantkumar Jaloji
Date Deposited: 24 Oct 2016 10:56
Last Modified: 24 Oct 2016 10:56
URI: http://eprints-bangaloreuniversity.in/id/eprint/7000

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