Biosafety Evaluation of 6,7‐Dihydroxy‐3‐(2‐Nitrophenyl)Coumarin in Human Cells

Abstract

Coumarins are considered a privileged scaffold in medicinal chemistry, as they may interact with biological macromolecules, presenting several pharmacological properties. Their potential makes them an object of study for the evaluation of their safety for humans, which is essential in the design of a potential drug. 6,7-Dihydroxy-3-(2-nitrophenyl)coumarin is a synthetic derivative with antioxidant properties, amongst other biological activities under study. The main goal of this study is to evaluate the potential cytotoxic and genotoxic effects of this molecule in peripheral blood mononuclear cells (PBMCs) and human hepatocellular carcinoma cells (HepG2/C3A). The results obtained for the cytotoxicity assays, evaluated by the resazurin assay, using concentrations between 0.1 and 50 μg/mL, showed that there is no decrease in cell viability for both cell lines. Regarding genotoxic assays, the data obtained by the comet assay and the micronucleus test, up to a concentration of 30 μg/mL, did not show significant DNA damage and/or chromosomal mutations for both cell types. Given these results, it can be concluded that 6,7-dihydroxy-3-(2-nitrophenyl)coumarin, up to a concentration of 30 μg/mL, does not present cytotoxic or genotoxic effects in human cells with and without hepatic metabolism. Considering that this family of coumarins, in general, presents their biological effect at low concentrations (mainly nanomolar range), the results obtained here encourage further studies with this molecule in drug discovery programs. 6,7-Dihydroxy-3-(2-nitrophenyl)coumarin is a new synthetic derivative with antioxidant properties, amongst other biological activities under study. The main goal of this study was to evaluate the potential cytotoxicity and genotoxicity of this molecule in human cells in vitro. Cytotoxicity assays in concentrations between 0.1 and 50 μg/mL showed no decrease in cell viability. Comet assay and the micronucleus test, up to a concentration of 30 μg/mL, did not show genetic toxicity.