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 β-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 μg/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 μg/mL) compared with negative and solvent control. MN frequencies were significantly increased in three applied concentrations (30, 15, 7.5 μg/mL) except lowest concentration (3.75 μg/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 β-lactam derivative can exert genotoxic and cytotoxic effects in peripheral human lymphocytes especially at high concentrations.
Highlights
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 β-lactam compound, chromosomal aberration (CA) and micronucleus (MN) tests were implemented in human peripheral blood lymphocytes
At present work; we aimed to investigate the genotoxic potential of this new compound with the chromosomal aberration (CA) and micronucleus (MN) tests in human peripheral blood lymphocytes
Summary
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. Since the beta-lactam and phthalazine derivatives are compounds that have a variety of activities and are the main skeleton of various pharmaceticals used for many years, the compounds carrying these groups in the same structure are likely to exhibit potent biological effects From this point of view, a new series of phthalazine substituted β-lactam derivatives synthesised at Sakarya University Chemistry Department. 1-(4-(3,3-dimethyl-1,6-dioxo2, 3,4,6,11,13-hexahydro-1H-indazolo[1,2b] phthalazine-13-yl)phenyl)-2-phenyl-azetidine-3yl-acetate (IV-b) found most active for human carbonic anydrase I and II enzyme inhibition (Berber et al 2015) Due to this biological activity, we thought it may be proposed as pharmaceutical raw material. In order to be able to use a synthetic substance as a medicine in the pharmaceutical industry; ligand-receptor interaction studies, pharmacokinetic analyzes, other toxicity tests including genotoxicity should be conducted In this regard, at present work; we aimed to investigate the genotoxic potential of this new compound with the chromosomal aberration (CA) and micronucleus (MN) tests in human peripheral blood lymphocytes
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