10.1371/journal.pone.0153155
Chakrabhavi Dhananjaya Mohan
Chakrabhavi
Dhananjaya Mohan
V. Srinivasa
V.
Srinivasa
Shobith Rangappa
Shobith
Rangappa
Lewis Mervin
Lewis
Mervin
Surender Mohan
Surender
Mohan
Shardul Paricharak
Shardul
Paricharak
Sefer Baday
Sefer
Baday
Feng Li
Feng
Li
Muthu K. Shanmugam
Muthu
K. Shanmugam
Arunachalam Chinnathambi
Arunachalam
Chinnathambi
M. E. Zayed
M. E.
Zayed
Sulaiman Ali Alharbi
Sulaiman Ali
Alharbi
Andreas Bender
Andreas
Bender
Gautam Sethi
Gautam
Sethi
Basappa
Basappa
Kanchugarakoppal S. Rangappa
Kanchugarakoppal
S. Rangappa
Trisubstituted-Imidazoles Induce Apoptosis in Human Breast Cancer Cells by Targeting the Oncogenic PI3K/Akt/mTOR Signaling Pathway
Public Library of Science
2016
PARP
Human Breast Cancer Cells
Akt 2 kinase
Na ïve Base classifier model
breast cancer cells
downregulated
CXCL
Akt 2 inhibitors
silico target prediction
VEGF
PDK
Oncogenic PI 3K Signaling Pathway Overactivation
PI 3K
synthesis
CIP
docking
2016-04-20 05:25:55
Dataset
https://plos.figshare.com/articles/dataset/Trisubstituted_Imidazoles_Induce_Apoptosis_in_Human_Breast_Cancer_Cells_by_Targeting_the_Oncogenic_PI3K_Akt_mTOR_Signaling_Pathway/3190366
<div><p>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 <i>in silico</i> 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.</p></div>