Evaluation of cytotoxic effects of several novel tetralin derivatives against Hela, MDA-MB-468, and MCF-7 cancer cells


1 Department of Pharmaceutical Chemistry, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Pharmaceutical Chemistry, Isfahan University of Medical Sciences, Isfahan; Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran


Background: The inhibitors of the enzymes estrone sulfatase and 17-β-hydroxysteroid dehydrogenase (17-β-HSD) could provide a means of blocking estrogen biosynthesis leading to regression of estrogen-dependent tumors. We evaluated the cytotoxicity of several tetralin derivatives, 2-(4-halo-phenylmethylene)-3,4-dihydronaphthalene-1-ones, as potential inhibitors of these two enzymes, on Hela, MDA-MB-468, and MCF-7 cancer cell lines.
Materials and Methods: The cell lines were cultured in RPMI medium and the cytotoxic effect of tested compounds (compounds 1 to 5) was screened at the concentrations of 0.1, 1, and 10 μM either alone or in combination with doxorubicin (100 μM), using MTT assay. The mixtures of cell suspension with solvent (1% DMSO in PBS) and doxorubicin (100 μM) were used as negative and positive controls, respectively. Each concentration of compounds was assayed in four wells and repeated in at least three independent experiments for each cell line. The cytotoxic effect of each particular concentration of tested compounds was expressed as the percent of cell survival.
Results: None of the compounds exhibited cytotoxic effect (reduction of cell survival to less than 50%) on tested cell lines. However, statistically significant reduction in cell survival was observed for some compounds against particular cell lines. Among all tested combinations of compounds with doxorubicin against cell lines, only compound 4 at 10 μM concentration showed synergistic cytotoxic effect with doxorubicin against Hela cells.
Conclusion: With the exception of compound 2, other tested compounds have potential for further cytotoxicity evaluation. Synthesizing other tetralin derivatives similar to compound 4 and studying their structure-activity relationships (SARs) would be encouraged.


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