Hypolipidaemic and antiplatelet activity of phenoxyacetic acid derivatives related to α-asarone

Abstract

The phenoxyacetic acid derivatives 1-6 [2-methoxy-4-(2-propenyl)phenoxyacetic acid (1); 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid (2); methyl 2-methoxy-4-(2-propenyl)phenoxyacetate (3); ethyl 2-methoxy-4-(2-propenyl)phenoxyacetate (4); methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (5); ethyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (6)] related to alpha-asarone have been reported previously as hypolipidaemic agents in diet-induced hyperlipidaemic mice. We have aimed to expand the pharmacological profile of these derivatives by investigating their hypolipidaemic activity in rats and mice under different experimental conditions. The antiplatelet activity was tested also in-vitro from blood derived from consenting healthy volunteers. In normolipidaemic rats, compounds 2, 3 and 5 at oral doses of 40 and 80 mg kg(-1) significantly decreased total cholesterol and LDL-cholesterol levels. Moreover, analogues 3 and 5 administered to hypercholesterolaemic rats at the same doses for seven days also produced a reduction in the content of these same lipoproteins. In neither case were the high-density lipoprotein cholesterol and triglyceride concentrations affected. However, practically all tested compounds were found to be hypocholesterolaemic agents, and were shown to effectively lower low-density lipoprotein cholesterol and triglyceride levels in Triton-induced hyperlipidaemic mice at oral doses of 50 and 100 mg kg(-1). In all tests, all animals appeared to be healthy throughout the experimental period in their therapeutic ranges. Triton-induced hypercholesterolaemic mice appeared to be a desirable model for this class of hypolipidaemic drugs. On the other hand, compounds 1, 2, 4 and 5 significantly inhibited ADP-induced aggregation in-vitro. These findings indicated that all of these compounds appeared to be promising for the treatment of human hyperlipidaemia and thrombotic diseases.

Hypolipidaemic activity of orally administered diphenyl diselenide in Triton WR-1339-induced hyperlipidaemia in mice

“…The nonionic detergent, Triton WR‐1339, has been used widely to block the uptake of triacylglycerol‐rich lipoproteins from plasma by peripheral tissues to produce acute hyperlipidaemia in animal models, which are often used for a number of objectives, in particular for screening natural or chemical hypolipidaemic drugs 1,20,21,28 . Experimental evidence supports the concept that Triton WR‐1339 physically alters very low density lipoproteins (VLDL), rendering them refractive to the action of lipolytic enzymes of blood and tissue 29 .…”

“…Triton WR‐1339 (an oxyethylated tertiary octyl phenol formaldehyde polymer), one of the well known nonionic detergents, has been used widely to produce acute hyperlipidaemia in animal models 20,21 . Thus, this study was designed to investigate a potential hypolipidaemic effect of (PhSe) 2 on Triton WR‐1339‐induced acute hyperlipidaemia in mice.…”

Separation ofcis- andtrans-Asarone fromAcorus tatarinowiiby Preparative Gas Chromatography

“…Further study indicated that activities of α -asarone in various animal seizure models [14] and against noise-stress effect [15] might be essentially accounted for by antioxidant properties. In addition, the hypolipidaemic [16–20] and radioprotective effects [21] of α -asarone were also been reported. Besides, β -asarone, which has toxic and sterilizing effects, shows potential for stored-product pest control [22].…”

Isolation, structure, and properties of quinone-aci tautomer of a phenol-nitro compound related to eugenoxyacetic acid

“…It is an odorless and tasteless compound with good antioxidant power and is considered to be nontoxic [1]. Eugenoxyacetic acid, 5-nitroeugenoxyacetic acid, and their methyl, ethyl esters are known to exhibit hypolipidaemic and antiplatelet activity and thus appear to be promising for the treatment of human hyperlipidaemia and thrombotic diseases [2][3][4]. In addition, several modified side chain eugenoxyacetic acids have been shown to exhibit antiviral and antimycobacterial activities [5,6].…”