Adamantyl-tethered-biphenylic compounds induce apoptosis in cancer cells by targeting Bcl homologs

Anusha, Sebastian and Mohan, C. D. and Ananda, H. and Baburajeev, C. P. and Shobith, R. and Mathai, Jessin and Fuchs, Julian E. and Li, Feng and Shanmugam, Muthu K. and Bender, A. and Sethi, Gautam and Basappa and Rangappa, K. S. (2016) Adamantyl-tethered-biphenylic compounds induce apoptosis in cancer cells by targeting Bcl homologs. Bioorganic & Medicinal Chemistry Letters, 26 (3). 1056 - 1060.

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Bcl homologs prominently contribute to apoptotic resistance in cancer cells and serve as molecular targets in treatment of various cancers. Herein, we report the synthesis of biphenyl-adamantane derivatives by a ligand free palladium on carbon based Suzuki reaction using diisopropylamine as a base for the coupling of adamantane based aryl chloride with a variety of aryl boronic acids. Among the biphenyl derivatives synthesized, compound 3′-(adamantan-1-yl)-4′-methoxy-1,1′-biphenyl-3-ol (AMB) displayed cytotoxic activity against hepatocellular carcinoma cell lines without significantly affecting the normal cell lines. Further, AMB caused increased accumulation of the HCC cells in subG1 phase, decreased the expression of Bcl-2, Bcl-xL, cyclin D1, caspase-3, survivin and increased the cleavage of PARP in a time-dependent manner. In silico molecular interaction studies between Bcl homologs and AMB showed that the biphenyl scaffold is predicted to form π–π interactions with Phe-101 and Tyr-105 and the adamantyl fragment is predicted to occupy another hydrophobic region in the kink region of the binding groove. In summary, we report on the synthesis and biological characterization of adamantyl-tethered biphenylic compounds that induce apoptosis in tumor cells most likely by targeting Bcl homologs.

Item Type: Article
Uncontrolled Keywords: Bcl homologs, Adamantyl-biphenyls, Apoptosis, Hepatoma, Molecular docking analysis
Subjects: C Chemical Science > Chemistry
Divisions: Department of > Chemistry
Depositing User: Manjula P Library Assistant
Date Deposited: 25 Jun 2019 06:07
Last Modified: 17 Jun 2022 10:36

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