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

Mohan, C. D. and Srinivasa, V. and Shobith, R. and Mervin, Lewis and Mohan, S. and Paricharak, Shardul and Baday, Sefer and Li, Feng and Shanmugam, Muthu K. and Chinnathambi, A. and Zayed, M. E. and Alharbi, Sulaiman Ali and Bender, Andreas and Sethi, Gautam and Basappa, and Rangappa, K. S. (2016) Trisubstituted-imidazoles induce apoptosis in human breast cancer cells by targeting the oncogenic PI3K/Akt/mTOR signaling pathway. PLoS One, 11 (4). pp. 1-15. ISSN 1932-6203

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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: Physical Sciences > Chemistry
Divisions: PG Campuses > Manasagangotri, Mysore > Chemistry
Depositing User: Praveen Kumari B.L
Date Deposited: 21 Jun 2017 09:47
Last Modified: 21 Jun 2017 09:47
URI: http://eprints.uni-mysore.ac.in/id/eprint/19542

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