2. Academic Validation
  3. Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents

Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents

  • Eur J Med Chem. 2016 Nov 29:124:608-621. doi: 10.1016/j.ejmech.2016.08.029.
Pankaj Sharma 1,  T Srinivasa Reddy 2,  Dinesh Thummuri 3,  Kishna Ram Senwar 1,  Niggula Praveen Kumar 1,  V G M Naidu 3,  Suresh K Bhargava 2,  Nagula Shankaraiah 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 2 Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne 3001, Australia.
  • 3 Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 4 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.
PMID: 27614408 DOI: 10.1016/j.ejmech.2016.08.029
Abstract

A series of new benzimidazole-thiazolidinedione hybrids has been synthesized and evaluated for their cytotoxic potential against a selected human Cancer cell lines of prostate (PC-3 and DU-145), breast (MDA-MB-231), lung (A549) and a normal breast epithelial cells (MCF10A). Among the tested compounds, 11p exhibited promising cytotoxicity with IC50 value of 11.46 ± 1.46 μM on A549 lung Cancer cell line and did not show significant toxicity on normal MCF10A cells. Lung Cancer cells (A549) have been used to know the mechanism of cell growth inhibition and Apoptosis inducing effect with compound 11p. The treatment of A549 cells with 11p showed typical apoptotic morphology like cell shrinkage, chromatin condensation and horseshoe shaped nuclei formation. Flow-cytometry analysis revealed the G2/M phase of cell cycle arrest in a dose dependent manner. Preliminary mechanistic studies suggested that the cell migration was inhibited through the disruption of F-actin protein. Acridine orange-ethidium bromide (AO-EB), DAPI, annexin V-FITC/propidium iodide, rhodamine-123 and MitoSOX assays suggested the induction of Apoptosis in A549 cells by compound 11p.

Keywords

Annexin; Apoptosis; Benzimidazole; Cell migration; MitoSOX; Thiazolidinedione.

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