Ellagitannins and hexahydroxydiphenoyl esters as inhibitors of vertebrate squalene epoxidase.

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Abe I, Kashiwagi Y, Noguchi H, Tanaka T, Ikeshiro Y, Kashiwada Y

Ellagitannins and hexahydroxydiphenoyl esters as inhibitors of vertebrate squalene epoxidase.

J Nat Prod. 2001 Aug;64(8):1010-4.

PubMed ID

11520216 [ View in PubMed

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Abstract

Ellagitannins isolated from various plant sources as well as newly synthesized n-alkyl (C(1)-C(18)) esters of hexahydroxydiphenyl (HHDP) dicarboxylic acid were evaluated as enzyme inhibitors of recombinant rat squalene epoxidase, a rate-limiting enzyme of cholesterol biosynthesis. Among the ellagitannins tested, pedunculagin (IC(50) = 2.0 microM) and eugeniin (IC(50) = 1.6 microM), both containing (S)-HHDP ester group(s), showed remarkable inhibition, which was more potent than those of previously reported substrate analogue inhibitors. Furthermore, ellagic acid (IC(50) = 2.0 microM), a bislactone formed by hydrolytic release of a HHDP group from ellagitannins, was also a good inhibitor of the enzyme. On the other hand, the synthetic HHDP esters with C(6) (IC(50) = 0.93 microM) and C(8) alkyl side chains (IC(50) = 0.83 microM) showed potent enzyme inhibition at the submicromolar concentration range, while esters with shorter chain lengths (C(1)-C(4)) and a C(18) ester exhibited moderate inhibition (IC(50) = 8-47 microM).

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ellagic acid	Squalene monooxygenase	Protein	Humans	Unknown	Inhibitor	Details