Hypolipidemic Activity of 3-N-(1′,8′-Naphthalimido)propionic Acid in Rodents

Hall, Iris H.; Chapman, James; Voorstad, P. J.; Cocolas, George H.

doi:10.1002/jps.2600730724

Cited by 14 publications

(6 citation statements)

References 22 publications

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“…Although it is difficult to extrapolate data from lipoprotein studies in mice to lipoprotein levels in humans, since the lipoprotein fractions are different [36], this study demonstrates that these α-asarone (1) analogs modulate the lipid levels in the lipoprotein fraction. Moreover, a noteworthy feature of the data revealed that the length of the side chain may be involved in modulating the bioactivity of these promising agents.…”

Section: Discussionmentioning

confidence: 86%

Synthesis and Hypolipidemic Activity of Modified Side Chain α-Asarone Homologues

Cruz¹,

Garduno²,

Salazar³

et al. 2011

Arzneimittelforschung

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A series of homologues of alpha-asarone (1), containing variable size and functionality on the side chain attached to the aromatic ring, has been subjected to a study of structure-activity relationship. For most of the prepared derivatives, either with a carbonyl (8a-8e), a hydroxy group (9a-9e), or with a conjugated double bond (10a-10d), significant effects on serum lipoprotein cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were displayed. The results showed an enhancement of the hypocholesterolemic activity as the length of the chain is decreased. Theoretical conformational and electrostatic potential analyses of I and olefins 10 suggest unfavorable steric interactions in the bulky superior side-chain homologues as the deactivating biological effect.

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Section: Discussionmentioning

confidence: 86%

Synthesis and Hypolipidemic Activity of Modified Side Chain α-Asarone Homologues

Cruz¹,

Garduno²,

Salazar³

et al. 2011

Arzneimittelforschung

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“…This was in contrast with compounds 3a and 3b, which display an increase of HDLcholesterol levels, although almost no effect was found in cholesterol dropping. Evidence has accumulated that the HDL fraction transports cholesterol out of the tissues to the liver for biliary excretion, hence a reduction of cholesterol levels would be associated with an enhancement of HDL-cholesterol [Hall et al, 1984]. Nevertheless, it appears that such a mechanism is not always involved in excreting cholesterol, since most of the clinically used hypolipidemic drugs (i.e., probucol) do not increase HDL-cholesterol content [Kannel and Sytkowsky, 1987].…”

Section: Discussionmentioning

confidence: 98%

“…As expected, a drop of LDL-cholesterol levels in serum is observed for compounds such as 5b, 5c, 6b, 6c and 7a, correlating with their effect in total cholesterol reduction. Lowdensity lipoproteins are responsible for lipid deposition in atherosclerotic plaque in blood vessels [Hall et al, 1984].…”

Section: Discussionmentioning

confidence: 99%

Hypolipidemic Activity of New Phenoxyacetic Derivatives Related to α‐Asarone with Minimal Pharmacophore Features

Cruz

Salazar

Garciafigueroa

et al. 2003

Drug Development Research

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Five new series of potential hypolipidemic agents 3-7 were synthesized, in order to establish the minimal pharmacophore features associated to the potent hypocholesterolemic activity of natural a-asarone (1) and synthetic clofibrate mimetic derivatives 2. The compounds were examined in hyperlipidemic male mice after oral administration of 25, 50, and 100 mg/Kg for 6 days. The isomeric series of acids and esters 3a-3c and 4a-4c were unexpectedly less active than the most simple structural isomeric compounds 5-7. This reveals that the phenoxyacetic acid scaffold carrying a hydrocarbon side chain, also found in derivatives 2, seems to be the most favorable lead for further development of potent hypolipidemic drugs. Drug Dev.

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“…Mice fed hypercholesterolaemic agents have been used frequently as a suitable model for exogenously-induced hypercholesterolaemia (Hall et al 1984;Poplawski et al 2000;Silva et al 2001). Drug responses observed in man are now being seen in such models (Krause & Princen 1998).…”

Section: Platelet Aggregation Activitymentioning

confidence: 99%

“…An exception, however, were compounds 3 and 5, which afforded a 50.3 and 88.7% increase, respectively, in normolipidaemic rats after 28 days of administration. Evidence has accumulated that the HDL fraction transports cholesterol out of the tissues to the liver for biliary excretion, hence a reduction of cholesterol levels would be associated with an enhancement of HDL-cholesterol (Hall et al 1984). However, clinical studies have shown that commercially available agents such as probucol do not significantly elevate HDL cholesterol concentration in plasma (Kannel & Sytkowsky 1987).…”

Section: Platelet Aggregation Activitymentioning

confidence: 99%

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

Pérez-Pasten

García

Garduño‐Siciliano

et al. 2006

Journal of Pharmacy and Pharmacology

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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.

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Hypolipidemic Activity of 3-N-(1′,8′-Naphthalimido)propionic Acid in Rodents

Cited by 14 publications

References 22 publications

Synthesis and Hypolipidemic Activity of Modified Side Chain α-Asarone Homologues

Synthesis and Hypolipidemic Activity of Modified Side Chain α-Asarone Homologues

Hypolipidemic Activity of New Phenoxyacetic Derivatives Related to α‐Asarone with Minimal Pharmacophore Features

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

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