Genotoxicity evaluation of a new phthalazine substituted beta-lactam derivative in human lymphocytes

Abstract

The aim of present study, to evaluate the genotoxic potential of 1-(4-(3,3-dimethyl-1,6-dioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2b] phthalazine-13yl) phenyl)-2-phenylazetidine-3-yl-acetate which was synthesised assuming that it may be a pharmaceutical raw material and found to inhibit human carbonic anhydrase I, II isozymes. To determine the genotoxic potential of this phthalazine substituted beta-lactam compound, chromosomal aberration (CA) and micronucleus (MN) tests were implemented in human peripheral blood lymphocytes. In these tests, lymphocyte cultures were treated with four concentrations (30, 15, 7.5, 3.75 mu g/mL) of test compound and simultaneously with negative control (sterile distilled water), solvent control (DMSO) positive control (MMC). According to our results, CA frequencies were significantly increased in two high applied concentrations (30, 15 mu g/mL) compared with negative and solvent control. MN frequencies were significantly increased in three applied concentrations (30, 15, 7.5 mu g/mL) except lowest concentration (3.75 mu g/mL) compared with solvent control. Mitotic indices were also affected by treatment with test compound. The obtained results provide evidence to demonstrate that new phthalazine substituted beta-lactam derivative can exert genotoxic and cytotoxic effects in peripheral human lymphocytes especially at high concentrations.