Synthesis and Evaluation of the Genotoxic Properties of Coumarin Derivative and its Complexes with Copper and Cobalt

Abstract

A new 6-hydroxy-4-methyl-5-(phenylazo)coumarin derivative (L) was successfully synthesized and characterized. Copper (II) and cobalt (II) complexes of L were also prepared and characterized using elemental (CHN) analysis, (FTIR), (¹H NMR), (MS), UV–Vi's spectroscopy, melting-point measurements, and molar conductivity. The spectroscopic and elemental analysis results supported the synthesized ligand and its metal complexes. The complexes exhibited low molar conductivity values, indicating their non-ionic nature. The genotoxic properties of 6-hydroxy-4-methylcoumarin, (L), and its complexes were evaluated using the alkaline comet assay by measuring the percentage of tail DNA (% Tail DNA). Hydrogen peroxide (H₂O₂) was used as a positive control (PC), while untreated cells served as the negative control (NC). The findings demonstrated that H₂O₂ induced the highest level of DNA damage, with a mean % Tail DNA of 32.04% in prostate cancer patient cells. In contrast, ligand L exhibited the lowest mean % Tail DNA (7.51%), significantly lower than both the H₂O₂-treated group (p < 0.0001) and the negative control group (p = 0.0043). The 6-hydroxy-4-methylcoumarin, cobalt (II), and copper (II) complex treatments also significantly reduced DNA damage compared with the H₂O₂ group, while their % Tail DNA values were not significantly different from those of the negative control or L. These findings indicate that L and its complexes did not increase DNA damage under the tested experimental conditions and may exhibit protective effects against oxidative DNA damage.