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

Pooja R. Kamath, Manu M. Joseph, Abdul Ajees Abdul Salam, Sreelekha T. Therakathinal, Dhanya Sunil, Subhankar Biswas, Karkala Sreedhara Ranganath Pai

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 apoptotic morphological alterations as observed in acridine orange/ethidium bromide and Hoechst staining. The wound healing migratory assay exhibited an intense impairment in the motility of MCF-7 cells on incubation with 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.

Original languageEnglish
Article numbere21962
JournalJournal of Biochemical and Molecular Toxicology
Volume31
Issue number11
DOIs
Publication statusPublished - 01-11-2017

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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