2. Academic Validation
  3. Conventional and microwave-assisted synthesis of new 1H-benzimidazole-thiazolidinedione derivatives: A potential anticancer scaffold

Conventional and microwave-assisted synthesis of new 1H-benzimidazole-thiazolidinedione derivatives: A potential anticancer scaffold

  • Eur J Med Chem. 2017 Sep 29:138:234-245. doi: 10.1016/j.ejmech.2017.06.035.
Pankaj Sharma 1,  T Srinivasa Reddy 2,  Niggula Praveen Kumar 1,  Kishna Ram Senwar 1,  Suresh K Bhargava 3,  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 Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne 3001, Australia. Electronic address: suresh.bhargava@rmit.edu.au.
  • 4 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.
PMID: 28668476 DOI: 10.1016/j.ejmech.2017.06.035
Abstract

A series of new benzimidazole bearing thiazolidinedione derivatives has been designed, synthesized by using conventional as well as microwave-assisted methods. Microwave-assisted synthesis caused a significant reduction in the reaction times and improvement in the yields of all the derivatives. All the new synthesized compounds were evaluated for their in vitro cytotoxic potential against selected human Cancer cell lines of breast (MDAMB-231), prostate (PC-3), cervical (HeLa), lung (A549) and bone (HT1080) along with a normal kidney cells (HeK-293T). The compounds 17n, 17p and 17q were found to be potent cytotoxic with IC50 values in the range of 0.096-0.63 μM on PC-3, HeLa, A549 and HT1080 Cancer cells. Most of the compounds have found to be safe on normal HeK-293T kidney cells in comparison to Cancer cells. The treatment of cells with 17p and 17q showed the typical apoptotic morphological features like fragmentation and shrinkage of nuclei. Further, test compounds resulted in inhibition of cell migration through disruption of F-actin protein assembly. Hoechst, DCFH-DA staining, mitochondrial membrane and annexin binding assays revealed that the Cancer cell proliferation was inhibited through induction of Apoptosis in A549 cells.

Keywords

Apoptosis; Benzimidazole; Cytotoxicity; Microwave; Thiazolidinedione.

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