Genotoxicity of α-asarone analogues Original Research Article

The role of cholesterol in the formation of atherosclerotic lesions during hypercholesterolemia has been confirmed. α-Asarone is a substance of a potent hypolipidemic activity which is isolated from plants. We previously described the synthesis of several α-asarone analogues exhibiting hypolipidemic and antiplatelet activity. Genotoxic activity of four selected α-asarone analogues was theoretically evaluated based on quantum-mechanical method for calculation of enthalpy of carbocations formation (ΔHR) according to the Testa’s method. In the present paper, we evaluated the mutagenic and genotoxic activity of α-asarone isomers 2–5 based on the reference Ames test and micronucleus test. Results obtained in the study show that tested isomers were non-mutagenic, however, they exhibited growing cytotoxic activity. Relationship between the heat of formation of their putative metabolic intermediates and mutagenic/genotoxic activity was not confirmed.