Compactin (ML-236B) and related compounds as potential cholesterol-lowering agents that inhibit HMG-CoA reductase

Endo, Akira

doi:10.1021/jm00382a001

Cited by 273 publications

(87 citation statements)

References 8 publications

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“…It should be noted that pannorin (1) and compactin analogs are similar in that both have a (5-lactone and hydrophobic decaline structure. Inhibitory activity of 1 was shown to be not comparable to that of compactin, and yet, the present results demonstrate a possible usefulness of its structure in synthesizing a new type of HMG-CoA reductase inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Pannorin, a new 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor produced by Chrysosporium pannorum.

et al. 1991

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Pannorin, a naphthopyrone that inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis, was isolated from a culture broth of Chrysosporium pannorum Ml0539 by solvent extraction, Bio-Gel P-6 column chromatography and The present communication deals with the isolation, characterization and biological activity ofpannorin (Fig. 1), a newtype ofHMG-CoA reductase inhibitor produced by a strain of Chrysosporiumpannorum. Taxonomy of Producing OrganismFungal strain Ml0539 that produces pannorin was isolated from a soil sample collected in Fussa City, Tokyo. Thecolonies on potato -glucose agar growrestrictedly, reaching a diameter of 2cmafter 2 weeks at 25°C, glabrous to powdery with scattered tufts of aerial growth, irregularly heaped, surface in brown; exudate in brown; reverse in light brown to brown. The fungus can grow at temperature range from 4 to 25°C with the growth optimum at about 15°C.The aleuriospores are borne at the tips, along the slides, or in an intercalary position on more or less erect conidiophores which branch verticillately at an acute angle. The conidia are subglobose to pyriform with smooth and hyaline walls, 2.5~3.5 x 2~3 /im in size (Fig. 2). From the characteristics described, the fungus was identified as a strain of C. pannorum (Link) Hughes M10539.4'5) Fig. 1. Structures of pannorin and compactin.

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Section: Discussionmentioning

confidence: 99%

Pannorin, a new 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor produced by Chrysosporium pannorum.

et al. 1991

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“…[2] Mevastatin is a specific and potent inhibitor of cholesterol biosynthesis, and also acts as an antifungal agent. [3] Mevastatin competitively inhibits the regulatory enzyme, 3-hydroxy-3-methylglutarylcoenzyme-A-reductase. Mevastatin is also a precursor of pravastatin, which is also an antihypercholesterolemic agent.…”

Section: Introductionmentioning

confidence: 99%

“…Mevastatin is also a precursor of pravastatin, which is also an antihypercholesterolemic agent. Among the few commercially used microbial strains for the production of mevastatin are P. citrinum, P. cyclopium and Aspergillus terreus [3][4][5] . In this study we have carried out experiments to optimize the physico chemical parameters and nutritional parameters to improve the production of mevasatin by sesame oil cake.…”

Section: Introductionmentioning

confidence: 99%

Optimization of Physico Chemical and Nutritional Parameters for the Production of Mevastatin Using Pencillium citrinum MTCC 1256

Rao¹

2013

iosrphr

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Abstract:-Statins are the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the class of drugs which are used in the treatment of hypercholesterolemia. They are the most efficient drugs for reducing plasma cholesterol. Mevastatin, also known as compactin is also a statin, catalyzes the conversion of HMG-CoA to mevanolate. Mevanolate is a required building block for cholesterol biosynthesis and mevastatin interferes with its production by acting as a reversible competitive inhibitor for HMG-CoA reductase and thus blocking the enzyme. The present study was carried out on the production of mevastatin by solid state fermentation with Pencillium citrinum MTCC 1256 using sesame oil cake at 28 o C. It deals with the study of parameters such as inoculum age, inoculum volume; nutritional suppliments such as carbon source, nitrogen source and their concentrations were optimized for the effective production of mevastatin.

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“…Known drug target proteins in the lipid control are HMG-Co A reductase in liver [19] and peroxisome proliferatoractivated receptors (PPARs) in adipocytes [20]. Many drugs targeting these proteins are used in the clinic and being developed.…”

Section: Introductionmentioning

confidence: 99%

FR177391, A New Anti-hyperlipidemic Agent from Serratia

et al. 2005

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Natural products with distinct biological activities are very promising molecular probes to dissect the novel pathways of biology. FR177391, a product of bacteria, was obtained as a natural compound possessing anti-hyperlipidemic effects. FR177391 enhances differentiation of mouse 3T3-L1 fibroblasts to adipocytes and reduces the circulating levels of triglyceride in C57BL/KsJ-db/db mice, a obese non-insulin-dependent diabetes mellitus animal model, although its mechanism of actions remained to be unknown. We report here that the target protein for FR177391 was identified to be protein phosphatase 2A (PP2A) by employing the method of affinity chromatography. FR177391 potently inhibited PP2A activity at nano molar concentration, and shared its binding pocket with a phosphatase inhibitor, okadaic acid. In addition to the phenotypic alterations, the enhancement for phosphorylation of extracellular signal-regulated kinase (ERK) protein was observed in the FR177391-treated 3T3-L1 cells. These results suggest that prolonged activation of ERK protein due to inhibition of its dephosphorylation by PP2A plays an important role in adipocyte maturation and regulation of the blood revels of lipids.

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Compactin (ML-236B) and related compounds as potential cholesterol-lowering agents that inhibit HMG-CoA reductase

Cited by 273 publications

References 8 publications

Pannorin, a new 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor produced by Chrysosporium pannorum.

Pannorin, a new 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor produced by Chrysosporium pannorum.

Optimization of Physico Chemical and Nutritional Parameters for the Production of Mevastatin Using Pencillium citrinum MTCC 1256

FR177391, A New Anti-hyperlipidemic Agent from Serratia

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