Trisubstituted-Imidazoles Induce Apoptosis in Human Breast Cancer Cells by Targeting the Oncogenic PI3K/Akt/mTOR Signaling Pathway | Zendy

Chakrabhavi Dhananjaya Mohan | Zendy; Venkatachalaiah Srinivasa | Zendy; Shobith Rangappa | Zendy; Lewis Mervin | Zendy; Surender Mohan | Zendy; Shardul Paricharak | Zendy; Sefer Baday | Zendy; Feng Li | Zendy; Muthu K. Shanmugam | Zendy; Arunachalam Chinnathambi | Zendy; Mohamed E. Zayed | Zendy; Sulaiman Ali Alharbi | Zendy; Andreas Bender | Zendy; Gautam Sethi | Zendy; Basappa Basappa | Zendy; Kanchugarakoppal S. Rangappa | Zendy

Open Access

Trisubstituted-Imidazoles Induce Apoptosis in Human Breast Cancer Cells by Targeting the Oncogenic PI3K/Akt/mTOR Signaling Pathway

Author(s) -

Chakrabhavi Dhananjaya Mohan,

Venkatachalaiah Srinivasa,

Shobith Rangappa,

Lewis Mervin,

Surender Mohan,

Shardul Paricharak,

Sefer Baday,

Feng Li,

Muthu K. Shanmugam,

Arunachalam Chinnathambi,

Mohamed E. Zayed,

Sulaiman Ali Alharbi,

Andreas Bender,

Gautam Sethi,

Basappa Basappa,

Kanchugarakoppal S. Rangappa

Publication year - 2016

Publication title -

plos one

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.99

H-Index - 332

ISSN - 1932-6203

DOI - 10.1371/journal.pone.0153155

Subject(s) - pi3k/akt/mtor pathway , protein kinase b , akt2 , cancer research , chemistry , akt1 , rptor , phosphorylation , survivin , signal transduction , kinase , cancer cell , carcinogenesis , apoptosis , microbiology and biotechnology , biology , cancer , biochemistry , genetics , gene

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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research