In vivo antigenotoxic potential and possible mechanism of action of selected 4-hydroxy-2H-chromen-2-one derivatives.
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.
Department of Biology and Ecology, Faculty of Science, University of Kragujevac, Serbia. msmaticsanja@yahoo.com
Sanja
S
Matić
Snežana
S
Stanić
Slavica
S
Solujić
Milan
M
Mladenović
Vladimir
V
Mihailović
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics*; D005020:Ethyl Methanesulfonate / Q000737:chemistry / Q000633:toxicity; D005260:Female; D005808:Genes, Recessive; D008297:Male; D008958:Models, Molecular; D009010:Monte Carlo Method; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity; D009154:Mutation / Q000187:drug effects; D009690:Nucleic Acid Conformation; D012730:Sex Chromosomes / Q000235:genetics
D016587:Antimutagenic Agents; D001578:Benzopyrans; D009153:Mutagens; D004247:DNA; D005020:Ethyl Methanesulfonate