TY - JOUR
T1 - Synthesis and hypolipidaemic evaluation of a series of α-asarone analogues related to clofibrate in mice
AU - Labarrios, Fernando
AU - Garduño, Leticia
AU - Vidal, Maria Del Rosario
AU - Garcia, Raul
AU - Salazar, Maria
AU - Martinez, Elizdath
AU - Diaz, Francisco
AU - Chamorro, German
AU - Tamariz, Joaquin
PY - 1999/1
Y1 - 1999/1
N2 - A series of α-asarone analogues related to clofibrate, containing an acetic acid group at C-2 of the aromatic ring, has been prepared as the acids or as the ethyl and methyl esters. The corresponding alcohols were also synthesized by reduction of the ethyl esters. The compounds were examined in hyperlipidaemic male mice to evaluate their ability to modify serum lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides after oral administration of 40 and 80 mg kg-1 for 6 days. Except for methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate at either dose, these clofibrate-related phenoxyacetic acid derivatives were found to have significant hypocholesterolaemic activity. Levels of low-density lipoprotein cholesterol and triglycerides were significantly reduced and those of high-density lipoprotein cholesterol were elevated. 2-Methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid was active at both doses in all the tests. Clofibrate (150 mg kg-1) was more potent at reducing low-density lipoprotein cholesterol. No activity was detected for the alcohol derivatives. These preliminary results suggest that this class of compound might have more promise as potential hypolipidaemic agents than other α-asarone derivatives. Further investigation and characterization should be performed to determine the mode of action of these agents on lipid metabolism.
AB - A series of α-asarone analogues related to clofibrate, containing an acetic acid group at C-2 of the aromatic ring, has been prepared as the acids or as the ethyl and methyl esters. The corresponding alcohols were also synthesized by reduction of the ethyl esters. The compounds were examined in hyperlipidaemic male mice to evaluate their ability to modify serum lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides after oral administration of 40 and 80 mg kg-1 for 6 days. Except for methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate at either dose, these clofibrate-related phenoxyacetic acid derivatives were found to have significant hypocholesterolaemic activity. Levels of low-density lipoprotein cholesterol and triglycerides were significantly reduced and those of high-density lipoprotein cholesterol were elevated. 2-Methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid was active at both doses in all the tests. Clofibrate (150 mg kg-1) was more potent at reducing low-density lipoprotein cholesterol. No activity was detected for the alcohol derivatives. These preliminary results suggest that this class of compound might have more promise as potential hypolipidaemic agents than other α-asarone derivatives. Further investigation and characterization should be performed to determine the mode of action of these agents on lipid metabolism.
UR - http://www.scopus.com/inward/record.url?scp=0033021868&partnerID=8YFLogxK
U2 - 10.1211/0022357991772015
DO - 10.1211/0022357991772015
M3 - Artículo
SN - 0022-3573
VL - 51
SP - 1
EP - 7
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
IS - 1
ER -