In vivo antigenotoxic potential and possible mechanism of action of selected 4-hydroxy-2H-chromen-2-one derivatives

Matić, S; Stanić, S; Solujić, S; Mladenović, M; Mihailović, V

HERO ID

4933191

Reference Type

Journal Article

Year

2012

HERO ID 4933191
In Press No
Year 2012
Title In vivo antigenotoxic potential and possible mechanism of action of selected 4-hydroxy-2H-chromen-2-one derivatives
Authors Matić, S; Stanić, S; Solujić, S; Mladenović, M; Mihailović, V
Journal Journal of Biochemical and Molecular Toxicology
Volume 26
Issue 8 (August 2012)
Page Numbers 322-330
Abstract The in vivo sex-linked recessive lethal test was carried out in Drosophila melanogaster to investigate whether or not five substituted 4-hydroxy-2H-chromen-2-ones can modulate the genotoxicity of the well-established mutagenic agent ethyl methanesulfonate (EMS). For this purpose, 3 days old Canton S males were treated with the potent mutagen EMS alone in concentration of 0.75 ppm, as well as in combination with one of the five 4-hydroxycoumarins, namely diethyl 2-(1-(4-hydroxy-2-oxo-2H-chromen-3-yl)ethylidene)malonate (2b), 3-(1-(4-hydroxy-2-oxo-2H-chromen-3-yl)ethylidene)pentane-2,4-dione (6b), 4-(4-(4-hydroxy-2-oxo-2H-chromen-3-yl)thiazol-2-ylamino) benzenesulfonic acid (4c), 4-hydroxy-3-(2-(2-nitropheny lamino)thiazol-4-yl)-2H-chromen-2-one (9c), and (E)-4-hydroxy-3-(1-(m-tolylimino)ethyl)-2H-chromen-2-one (5d), in concentration of 70 ppm. The frequency of germinative mutations increased significantly after the treatment with EMS and decreased after treatments with coumarins. The maximum reduction was observed after treatments with 2b, 6b, 4c, and 5d. By the formation of hydrogen bonds or electrostatic interactions with O(6) of DNA guanine, tested coumarins prevent EMS-induced alkylation. The results indicate a protective role of five 4-hydroxycoumarins under the action of a strong mutagen.
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Keyword Index Medicus