TY - JOUR
T1 - In vitro genotoxic evaluation of three α-asarone analogues
AU - Cassani-Galindo, M.
AU - Madrigal-Bujaidar, E.
AU - Chamorro, G.
AU - Díaz, F.
AU - Tamariz, J.
AU - Espinosa-Aguirre, J. J.
PY - 2005/6
Y1 - 2005/6
N2 - α-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 α-asarone were prepared in order to maintain the same pharmacological properties but with low toxicity. In this study we evaluated the potential of three α-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 μg/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.
AB - α-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 α-asarone were prepared in order to maintain the same pharmacological properties but with low toxicity. In this study we evaluated the potential of three α-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 μg/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.
KW - Ames test
KW - Mutagenicity in vitro
KW - SCE on lymphocyte
KW - α-Asarone analogues
UR - http://www.scopus.com/inward/record.url?scp=17044380129&partnerID=8YFLogxK
U2 - 10.1016/j.tiv.2005.01.007
DO - 10.1016/j.tiv.2005.01.007
M3 - Artículo
SN - 0887-2333
VL - 19
SP - 547
EP - 552
JO - Toxicology in Vitro
JF - Toxicology in Vitro
IS - 4
ER -