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Retracted : Bisindole‐oxadiazole hybrids, T3P ® ‐mediated synthesis, and appraisal of their apoptotic, antimetastatic, and computational Bcl‐2 binding potential
Author(s) -
Kamath Pooja R.,
Joseph Manu M.,
Abdul Salam Abdul Ajees,
T. Therakathinal Sreelekha,
Sunil Dhanya,
Biswas Subhankar,
Pai Karkala Sreedhara Ranganath
Publication year - 2017
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21962
Subject(s) - acridine orange , cytotoxicity , chemistry , apoptosis , ethidium bromide , oxadiazole , cancer cell , in vitro , stereochemistry , biochemistry , biology , cancer , organic chemistry , dna , genetics
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‐(1 H ‐indol‐3‐ylmethyl)‐1,3,4‐oxadiazol‐2‐yl]‐1 H ‐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.