Genotoxicity of two new carbazole derivatives with antifungal activity.

Autor: Zhanataev AK; Zakusov Research Institute of Pharmacology, 8 Baltiyskaya St., Moscow, 125315, Russia., Eremina NV; Zakusov Research Institute of Pharmacology, 8 Baltiyskaya St., Moscow, 125315, Russia; Panacela Labs LLC, 12,Blvd.1, Krivokolennyi Per., Moscow, 101000, Russia. Electronic address: neremina@panacelalabs.com., Chayka ZV; Zakusov Research Institute of Pharmacology, 8 Baltiyskaya St., Moscow, 125315, Russia., Kazey VI; Panacela Labs LLC, 12,Blvd.1, Krivokolennyi Per., Moscow, 101000, Russia., Andrianova EL; Panacela Labs LLC, 12,Blvd.1, Krivokolennyi Per., Moscow, 101000, Russia., Purmal AA; Сleveland BioLabs, Inc., 73 High St., Buffalo, NY, 14203, USA., Rydkina EB; Сleveland BioLabs, Inc., 73 High St., Buffalo, NY, 14203, USA., Durnev AD; Zakusov Research Institute of Pharmacology, 8 Baltiyskaya St., Moscow, 125315, Russia.
Jazyk: angličtina
Zdroj: Mutation research. Genetic toxicology and environmental mutagenesis [Mutat Res Genet Toxicol Environ Mutagen] 2017 Apr; Vol. 816-817, pp. 24-31. Date of Electronic Publication: 2017 Apr 01.
DOI: 10.1016/j.mrgentox.2017.03.004
Abstrakt: The class of carbazoles includes compounds with high biological activities and broad spectra of action. PLX01107 and PLX01008 are xenomycins, a new subclass of antimicrobial carbazole derivatives demonstrating strong antifungal activity in vitro. We performed three tests, a bacterial reverse mutation assay (Ames test), in vitro cytokinesis-block micronucleus assay, and chromosome aberration test in mouse bone marrow cells, to investigate the possible genotoxicity of these compounds. Despite their structural similarity, the two compounds had different genotoxicity profiles. PLX01008 showed positive effects in all assays. PLX01107 showed no mutagenicity in the Ames test but demonstrated strong cytogenetic activity in vitro and in vivo. PLX01107 was also tested in the in vivo alkaline comet assay, where a weak but statistically significant increase in DNA damage was seen in liver cells 24h after treatment. Significantly increased levels of formamidopyrimidine DNA glycosylase (FPG)-sensitive sites were found in bone marrow cells of PLX01107-treated mice (FPG-modified comet assay), suggesting induction of oxidative or alkylation damage to DNA.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: