Genotoxicity of alpha-asarone analogues.
The role of cholesterol in the formation of atherosclerotic lesions during hypercholesterolemia has been confirmed. alpha-Asarone is a substance of a potent hypolipidemic activity which is isolated from plants. We previously described the synthesis of several alpha-asarone analogues exhibiting hypolipidemic and antiplatelet activity. Genotoxic activity of four selected alpha-asarone analogues was theoretically evaluated based on quantum-mechanical method for calculation of enthalpy of carbocations formation (DeltaH(R)) according to the Testa's method. In the present paper, we evaluated the mutagenic and genotoxic activity of alpha-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.
Karwicka
Ewa
E
National Medicines Institute, Biochemistry and Biopharmaceuticals Department, Chełmska 30/34, 00-725 Warszawa, Poland. ewa@il.waw.pl
Marczewska
Jadwiga
J
Anuszewska
Elzbieta
E
Łozowicka
Bozena
B
Chilmonczyk
Zdzisław
Z
D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D001711:Biotransformation / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006358:Hot Temperature; D006801:Humans; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D007536:Isomerism; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D015162:Micronucleus Tests; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D012854:Sister Chromatid Exchange / Q000187:drug effects
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D000960:Hypolipidemic Agents; D009153:Mutagens; C012195:asarone