In vitro genotoxic evaluation of three alpha-asarone analogues.
alpha-Asarone has shown a significant capacity to reduce the level of lipids, including cholesterol. However, several toxic and genotoxic studies have determined that its use may pose a risk to human health. Therefore, a series of compounds structurally analogous to alpha-asarone were prepared in order to maintain the same pharmacological properties but with low toxicity. In this study we evaluated the potential of three alpha-asarone analogues to induce mutagenicity using the Ames test (strains TA98 and TA100 in the presence of metabolic activation), as well as the induction of sister chromatid exchanges (SCE) in cultured human lymphocytes. The tested compounds were: 1-(2,4,5-trimethoxyphenyl)propan-1-one (D1), 1-(2-chloro-4,5-dimethoxyphenyl)propan-1-one (D2), and 1-(4,5-dimethoxy-2-nitrophenyl)propan-1-ol (D3). The results in the first assay showed no mutagenic effect for the three tested analogues; in the TA100 strain, certain cytotoxicity did appear in the case of D2 and D3 only at high concentrations. In regard to the SCE assay, compounds D1 and D2 presented no statistical differences in comparison with the control culture values; however, the high dose of D3 (300 microg/ml) produced a significant increment in SCE (68% above the control value). With respect to the mitotic index and the cellular proliferation kinetics, we observed a reduction when compounds D2 and D3 were used at the higher concentrations. Our results encourage further preclinical studies of these compounds in both in vitro and in vivo models (particularly for analogues D1 and D2), to determine their toxicological profile and establish the possibility of using them in humans.
Cassani-Galindo
M
M
Laboratorio de Genética, Escuela Nacional de Ciencias, Biológicas, I.P.N., Carpio y Plan de Ayala. Sto. Tomás., México, DF cp 11340, México.
Madrigal-Bujaidar
E
E
Chamorro
G
G
Díaz
F
F
Tamariz
J
J
Espinosa-Aguirre
J J
JJ
D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D000960:Hypolipidemic Agents / Q000633:toxicity*; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects; D008940:Mitotic Index; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012854:Sister Chromatid Exchange
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D000960:Hypolipidemic Agents; D009153:Mutagens; C012195:asarone