Genotoxicity of potent antiviral 1-[(2-aminophenyl)thio]-1-phenyl-2-nitrobutane derivatives designed as drug agents

Abstract

Objective: Genotoxic potentials of six selected nitrobutane (I) derivatives designed as drug agents were tested here for the first time using umu-microplate test system. An important principle in drug development is to perform safety tests of previously determined significant drug activity in in vitro assays. This may be even more crucial than its efficiency in terms of experimental conditions, since it is important in chemotherapy to treat without risk for the patient. Methods: Umu-microplate test system is especially designed for detecting the mutagenicity of nitro compounds. 1-[(2-aminophenyl)thio]-1-phenyl-2-nitrobutane (I) derivatives involve nitro groups. Therefore umu-microplate test system has been chosen for our analysis. Evaluation of the SOS inducing activity of the tested compounds was examined with the umumicroplate test system using Salmonella typhimurium NM1011 (overexpressed NR (nitroreductase)) and S.typhimurium NM2009 (overexpressed O-At (O-acethyltransferase))strains which are sensitive to nitro compounds. Chlorophenol red-β-D-galactopyranoside (CPRG) and O-nitrophenyl-β-Dgalactopyranoside (ONPG) were used as substrate in the enzyme assays and also the well-known genotoxic nitro compound, 4-nitroquinoline 1-oxide (4NQO), was the positive control in the test. Results: Although the β-galactosidase activities with using CPRG were three fold higher than ONPG, parallel results were obtained for both substrates and strains with all compounds tested. For all compounds, the induction of umuC gene expression was found to be almost the same for the strains that overexpress NR and O-At. The derivatives tested didn’t caused an evident induction in both strains overexpressed NR and O-At enzymes which have a role in metabolic activation mechanism of nitro compunds. Conclusion: Our study showed that, 1-[(2-aminophenyl)thio]-1-phenyl-2-nitrobutane derivatives have no genotoxic effects in this test system. This result is a very important data making them a potential drug candidate.