Design, synthesis and evaluation biological effects of thiazolidinedione derivatives on human non-small-cell lung cancer a549 by using mtt assay

Sedighe Mirbagheri,1,* Fatemeh safari,2 Asadollah mohammadi,3 Mohammad nikpassand,4 Hossein ghafoori,5

1. Department of Biology, Science and Research Branch, Islamic Azad university
2. Departmentof Biology, Faculty of Science, University of Guilan
3. Department of Chemistry, Faculty of Sciences, University of Guilan
4. Department of Chemistry, Rasht Branch, Islamic Azad University
5. Departmentof of biochemistry, Faculty of Science, University of Guilan

Abstract

Introduction

Cancer is one of the common causes of death in the world and treatment of the cancer is the most important challenge for researchers. the heat shock proteins (hsp) family is a group of molecular chaperones to assist protein folding, modification, and transportation. heat shock proteins are created by cells. while they can help the cells to protect cells some diseases including artery problems or cancer. hsp are named according to their weight. the range of molecular chaperones varies from 10 to over 100 kda. also, hsps are widely expressed in human cancers and play important roles in proliferation, invasion, metastasis, apoptosis of cancer cells. apoptosis is the important mechanism to control the cancer cells. it was found that hsps are highly expressed in cancer cells and thereby, hsps are supposed to play important roles to induce apoptosis in cancer cells. among hsps, we are interested to focus on hsp70 as a potential inducer of apoptosis. hsp70 protein contains highly conserved domain structures including nucleotide binding domain (nbd) which is atp binding site. herein, we designed and synthesised thiazolidinedione derivatives. thiazolidinedione derivatives may inhibit hsp70 protein by occupy the atp binding site in nbd domain. finally, we evaluated biological effects of thiazolidinedione derivatives on lung cancer cell line a549 by using mtt assay.

Methods

In this study, a new series of thiazolidinedione derivatives (mb1-6) were synthesized by reflux condenser. during synthesis, tlc was used to confirm the formation of compounds and their purity. the structures of the compounds were confirmed by ft-ir, c nmr, and h nmr. we investigate the effects of 6 samples of thiazolidinedione derivatives in different concentrations of 50µm to 1000µm with a three-time repeat count on the cells of the human non-small-cell lung cancer a549 cancer. dmso as negative control have been used to determine the accuracy of the work. mtt assay was used to measure the toxicity of the compounds.

Results

According to the obtained results, the compounds mb 1, mb3 and mb6 exhibited strong inhibitory activities with ic50 values of 0.5, 0.5, and 0.9 mm, respectively, compared to the positive control cisplatin (10 µg/ml).

Conclusion

Further studies are necessary for detailed. the results shown the metylen (ch2) of thiazolidinedione and formyl (-cho) group of our aldehyde are react with them and new thiazolidinedione derivative was synthesized. also derived compounds mb1, mb3 and mb6 significantly inhibit proliferation of aβ4 cells.

Keywords

Hsp70 protein, thiazolidinedione derivatives, cancer cell, mtt assay