- Trisubstituted-imidazoles induce apoptosis in human breast cancer cells by targeting the oncogenic PI3K/Akt/mTOR signaling pathway
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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:
- 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.
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- Potent antimicrobial activity of 3-(4,5-diaryl-1H-imidazol-2-yl)-1H-indole derivatives against methicillin-resistant Staphylococcus aureus
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A new series of antimicrobial derivatives [3-(4,5-diaryl-1H-imidazol-2-yl)- 1H-indole)] have been synthesized with potent activity against strains of Staphylococcus aureus, including methicillin-resistant strains (MRSA). Compound 17 [3-(4,5-bis(4-fluoroph
- Al-Qawasmeh, Raed A.,Huesca, Mario,Nedunuri, Venkata,Peralta, Robert,Wright, Jim,Lee, Yoon,Young, Aiping
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experimental part
p. 3518 - 3520
(2010/08/20)
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- ARYL IMIDAZOLES AND THEIR USE AS ANTI-CANCER AGENTS
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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
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Page/Page column 78-79
(2008/06/13)
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- 2,4,5-TRISUBSTITUTED IMIDAZOLES AND THEIR USE AS ANTI-MICROBIAL AGENTS
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The present invention provides therapeutically effective 2,4,5-trisubstituted imidazole compounds, methods of preparing the same, and compositions comprising the compounds alone or in combination with other agents. The present invention further provides f
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