Chemical features of flavonols affecting their genotoxicity. Potential implications in their use as therapeutical agents

• Published in: Chemico-biological interactions 2000-01, Vol.124 (1), p.29-51
• Main Authors: Duarte Silva, I, Gaspar, J, Gomes da Costa, G, Rodrigues, A.S, Laires, A, Rueff, J
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Cattle; Cell Line; Cricetinae; Cricetulus; Deoxyribose - metabolism; Drug Design; Flavonoids; Flavonoids - pharmacokinetics; Flavonoids - toxicity; Flavonols; Genotoxicity; Hydroxyl Radical - metabolism; Liver - enzymology; Liver - metabolism; Male; Mutagenicity Tests; Mutagens - pharmacokinetics; Mutagens - toxicity; Pro-oxidants; Rats; Rats, Wistar; Reactive oxygen species; Reactive Oxygen Species - metabolism; Structure–activity
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/S0009-2797(99)00139-8

Flavonls are natural compounds present in edible plants and possess several biological activities that can be useful in drug design. Conversely some of these compounds have been shown to be genotoxic to prokaryotic and eukaryotic cells. In this study we tried to establish the chemical features responsible for the genotoxicity of flavonols and to study the conditions that can modulate their genotoxicity namely pH, the presence of antioxidants and metabolism. We assessed the induction of revertants in Salmonella typhimurium TA98 and the induction of Chromosomal aberrations in V79 cells by eight different flavonols and one catechin in the presence and in the absence of metabolizing systems. We have also studied the generation of hydroxyl radical by these flavonoids using the deoxyribose degradation assay. The results obtained in this study suggest that flavonols having a free hydroxyl group at position 3 of the C ring, a free hydroxyl group at position 7 of the A ring and a B ring with a catechol or pyrogallol structure, or a structure that after metabolic activation is transformed into a catechol or a pyrogallol, are flavonols whose genotoxicity in eukaryotic cells depends on their autooxidation. These flavonols can autooxidize when the pH value is slightly alkaline, such as in the intestine, and therefore can induce genotoxicity in humans. Given the above mentioned considerations it is necessary to clarify the mechanisms and the conditions that mediate the biological effects of flavonols before considering them as therapeutical agents.