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

Creative Commons License

Aygun B., BERBER A. A., DOĞANCI M. A., BERBER N., Sen S., Yildiz E., ...More

ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS, vol.94, no.1, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 94 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1590/0001-3765202120191476
  • Journal Name: ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, Animal Behavior Abstracts, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Communication Abstracts, EMBASE, INSPEC, MEDLINE, Metadex, Veterinary Science Database, zbMATH, Directory of Open Access Journals, Civil Engineering Abstracts
  • Keywords: chromosomal aberration, carbonic anhydrase, beta-lactam, micronucleus, phthalazine, toxicology, CARBONIC-ANHYDRASE INHIBITORS, CHROMOSOMAL-ABERRATIONS, ANTIBIOTICS, CYTOTOXICITY, INVITRO, ANTICONVULSANT, PYRIDAZINONE, BIOMARKERS, AMPICILLIN, EXPOSURE
  • Çanakkale Onsekiz Mart University Affiliated: Yes

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.