Abstract
A series of cinnamic acid derivatives were synthesized and their biological abilities on lipoprotein metabolism were examined. Among the tested compounds, 4-hydroxycinnamic acid (l-phenylalanine methyl ester) amide (1) and 3,4-dihydroxyhydrocinammic acid (l-aspartic acid dibenzyl ester) amide (2) inhibited human acyl-CoA:cholesterol acyltransferase-1 and -2 activities with apparent IC(50) around 60 and 95 microM, respectively. Compounds 1 and 2 also served as an antioxidant against copper mediated low-density lipoproteins (LDL) oxidation with apparent IC(50)=52 and 3 microM, compound 1 and 2, respectively. Additionally, decrease of HDL-particle size under presence of LDL was inhibited by the 1 at 307 microM of final concentration. Treatment of the 1 or 2 did not influence normal growth of RAW264.7 without detectable cytotoxic activity from a cell viability test. These results suggest that the new cinnamic acid derivatives possess useful biological activity as an anti-atherosclerotic agent with inhibition of cellular cholesterol storage and transport by the both ACAT, inhibition of LDL-oxidation, HDL particle size rearrangement.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Alanine / analogs & derivatives*
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Alanine / chemical synthesis
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Alanine / pharmacology*
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Alanine / toxicity
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Animals
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Antioxidants / chemical synthesis
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Antioxidants / pharmacology*
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Antioxidants / toxicity
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Aspartic Acid / analogs & derivatives*
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Aspartic Acid / chemical synthesis
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Aspartic Acid / pharmacology*
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Aspartic Acid / toxicity
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Cell Line
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Cell Survival / drug effects
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Cinnamates / chemical synthesis
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Cinnamates / pharmacology*
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Cinnamates / toxicity
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Electrophoresis, Agar Gel
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Humans
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Lipoproteins, HDL / chemistry
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Lipoproteins, HDL / metabolism*
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Lipoproteins, LDL / antagonists & inhibitors*
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Lipoproteins, LDL / chemistry
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Lipoproteins, LDL / metabolism
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Mice
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Phenylalanine / analogs & derivatives*
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Phenylalanine / chemical synthesis
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Phenylalanine / pharmacology*
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Phenylalanine / toxicity
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Rats
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Sterol O-Acyltransferase / antagonists & inhibitors*
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Sterol O-Acyltransferase 2
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Structure-Activity Relationship
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Thiobarbituric Acid Reactive Substances
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Time Factors
Substances
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3,4-dihydroxyhydrocinammic acid (L-alanine methyl ester) amide
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3,4-dihydroxyhydrocinammic acid (l-aspartic acid dibenzyl ester) amide
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4-hydroxycinnamic acid (l-phenylalanine methyl ester) amide
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Antioxidants
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Cinnamates
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Lipoproteins, HDL
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Lipoproteins, LDL
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Thiobarbituric Acid Reactive Substances
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Aspartic Acid
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Phenylalanine
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Sterol O-Acyltransferase
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sterol O-acyltransferase 1
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Alanine