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

Creative Commons License

Aygün B., Berber A. A., Dogancı M. A., Berber N., Şen S., Yıldız E., ...Daha Fazla

ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS, cilt.94, sa.1, ss.1-12, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 94 Sayı: 1
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1590/0001-3765202120191476
  • Dergi Adı: ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS
  • Derginin Tarandığı İndeksler: 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
  • Sayfa Sayıları: ss.1-12
  • Anahtar Kelimeler: chromosomal aberration, carbonic anhydrase, beta-lactam, micronucleus, phthalazine, toxicology, CARBONIC-ANHYDRASE INHIBITORS, CHROMOSOMAL-ABERRATIONS, ANTIBIOTICS, CYTOTOXICITY, INVITRO, ANTICONVULSANT, PYRIDAZINONE, BIOMARKERS, AMPICILLIN, EXPOSURE
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

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.