Bisindole-oxadiazole hybrids, T3P R � -mediated synthesis, and appraisal of their apoptotic, antimetastatic, and computational Bcl-2 binding potential

Kamath, Pooja R and Joseph, Manu M and Salam, Abdul Ajees Abdul and Sreelekha, T T and Sunil, Dhanya and Biswas, Subhankar and Pai, Ranganath Sridhar (2017) Bisindole-oxadiazole hybrids, T3P R � -mediated synthesis, and appraisal of their apoptotic, antimetastatic, and computational Bcl-2 binding potential. Journal of Biochemical and Molecular Toxicology, e21962 (7). pp. 1-11. ISSN 1095-6670

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Abstract

In the pursuit of novel anticancer leads, new bisindole-oxadiazoles were synthesized using propyl phosphonic anhydride as a mild and efficient reagent. The molecule, 3-[5-(1H-indol-3-ylmethyl)- 1,3,4-oxadiazol-2-yl]-1H-indole (3a) exhibited selective cytotoxicity to MCF-7 cells with a cell cycle arrest in the G1 phase. The mechanism of cytotoxicity of 3a involved caspase-2-dependent apoptotic pathway with characteristic apoptoticmorphological alterations as observed in acridine orange/ethidium bromide and Hoechst staining. The wound healing migratory assay exhibited an intense impairment in themotility ofMCF-7 cells on incubationwith 3a.Docking simulations with anti-apoptotic protein Bcl-2, which is also involved in cancer metastasis displayed good affinity and high binding energy of 3a into the well characterized BH3 binding site. The positive correlation between the Bcl-2 binding studies and the results of in vitro investigations exemplifies compound 3a as a lead molecule exhibiting MCF-7 differential cytotoxicity via apoptotic mode of cell death in addition to its anti-metastatic activity

Item Type: Article
Uncontrolled Keywords: apoptosis, bisindole-oxadiazole, Bcl-2, caspases,migration
Subjects: Engineering > MIT Manipal > Chemistry
Depositing User: MIT Library
Date Deposited: 01 Aug 2017 04:59
Last Modified: 01 Aug 2017 04:59
URI: http://eprints.manipal.edu/id/eprint/149452

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