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Title: Bisindole-Oxadiazole Hybrids, T3P®-Mediated Synthesis, and Appraisal of Their Apoptotic, Antimetastatic, and Computational Bcl-2 Binding Potential
Authors: Pooja, R K
Joseph, M M
Abdul Salam, A A
Sreelekha, T T
Dhanya, S
Biswas, S
Pai, K S R
Keywords: apoptosis
Issue Date: Nov-2017
Publisher: Wiley
Citation: Journal of Biochemical and Molecular Toxicology, 31(11):e21962
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.
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