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

1 Citation (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

Fingerprint

Oxadiazoles
MCF-7 Cells
Cytotoxicity
Caspase 2
Acridine Orange
Apoptosis Regulatory Proteins
Ethidium
Anhydrides
G1 Phase
Cell Cycle Checkpoints
Wound Healing
Molecules
Cell Death
Binding Sites
Cell death
Staining and Labeling
Neoplasm Metastasis
Binding energy
Assays
Cells

All Science Journal Classification (ASJC) codes

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

Cite this

@article{a065076ab7034469bb28bfffba2231e0,
title = "Bisindole-oxadiazole hybrids, T3P{\circledR}-mediated synthesis, and appraisal of their apoptotic, antimetastatic, and computational Bcl-2 binding potential",
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.",
author = "Kamath, {Pooja R.} and Joseph, {Manu M.} and {Abdul Salam}, {Abdul Ajees} and Therakathinal, {Sreelekha T.} and Dhanya Sunil and Subhankar Biswas and Pai, {Karkala Sreedhara Ranganath}",
year = "2017",
month = "11",
day = "1",
doi = "10.1002/jbt.21962",
language = "English",
volume = "31",
journal = "Journal of Biochemical and Molecular Toxicology",
issn = "1095-6670",
publisher = "John Wiley and Sons Inc.",
number = "11",

}

Bisindole-oxadiazole hybrids, T3P®-mediated synthesis, and appraisal of their apoptotic, antimetastatic, and computational Bcl-2 binding potential. / Kamath, Pooja R.; Joseph, Manu M.; Abdul Salam, Abdul Ajees; Therakathinal, Sreelekha T.; Sunil, Dhanya; Biswas, Subhankar; Pai, Karkala Sreedhara Ranganath.

In: Journal of Biochemical and Molecular Toxicology, Vol. 31, No. 11, e21962, 01.11.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bisindole-oxadiazole hybrids, T3P®-mediated synthesis, and appraisal of their apoptotic, antimetastatic, and computational Bcl-2 binding potential

AU - Kamath, Pooja R.

AU - Joseph, Manu M.

AU - Abdul Salam, Abdul Ajees

AU - Therakathinal, Sreelekha T.

AU - Sunil, Dhanya

AU - Biswas, Subhankar

AU - Pai, Karkala Sreedhara Ranganath

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85033212481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033212481&partnerID=8YFLogxK

U2 - 10.1002/jbt.21962

DO - 10.1002/jbt.21962

M3 - Article

C2 - 28724188

AN - SCOPUS:85033212481

VL - 31

JO - Journal of Biochemical and Molecular Toxicology

JF - Journal of Biochemical and Molecular Toxicology

SN - 1095-6670

IS - 11

M1 - e21962

ER -