Lanosterol

About: Lanosterol is a research topic. Over the lifetime, 1239 publications have been published within this topic receiving 36737 citations. The topic is also known as: (3β)-lanosta-8,24-dien-3-ol & (3β,20R)-lanosta-8,24-dien-3-ol.

Inhibition of cholesterol absorption by neomycin, benzodiazepine derivatives and ketoconazole.

Abstract: Neomycin and a benzodiazepine derivative (RO16-0521) inhibit similarly cholesterol absorption in man but the serum cholesterol level is reduced only by neomycin. Reason(s) for the difference are unknown. Ketoconazole inhibits 14α-demethylation of lanosterol so that cholesterol synthesis is reduced. The agent inhibits also cholesterol absorption. The serum cholesterol level is reduced by about 20%, the lowering being potentiated by a simultaneous cholestyramine treatment.

Dioxidosqualenes : characterization and activity as inhibitors of 2,3-oxidosqualene-lanosterol cyclase

Abstract: The preparation and characterization of dioxidosqualenes 4-10 is reported. Treatment of the appropriate epoxysqualene 1, 2, or 3 with NBS followed by chromatographic purification afforded the corresponding epoxybromohydrins 11-14 as diastereomeric mixtures, with the exception of compound 11, which could be separated into the respective racemates 11a and 11b. Further dehydrobromination with NaH in THF led to the respective dioxidosqualenes 4-8 in good conversion yields. Dioxides 9 and 10 were isolated from the crude reaction mixture of the treatment of epoxide 2 with dimethyldioxirane. Characterization of compounds 4-10 was carried out by combining 1 H and 13 C NMR spectral means with positive GC-MS-CI analysis. The GC-MS-CI analysis inclued the identification of the carbonyl compounds resulting from the cleavage of dioxido derivatives with periodic acid. Finally, data on the activity of dioxidosqualenes as oxidosqualene-lanosterol cyclase (OSLC) inhibitors in rat liver microsomes are also presented. In this respect, 2,3:18,19-dioxidosqualene was found to be the best inhibitor within the compounds assayed (IC 50 =0.11μM), although other dioxides also exhibited a potent inhibitory activity. The fact that these compounds could be potentially generated in an organism constitutes a remarkable difference relative to other OSLC inhibitors described to date

Inhibition of cholesterol biosynthesis by dehydroepiandrosterone in lactating mammary gland.

Abstract: The addition of dehydroepiandrosterone (DHA) 3 × 10−5 to 3 × 10−4m to minced guinea pig mammary gland incubated with acetate-l-14C resulted in a strong inhibition of the labeling of squalene, lanosterol and cholesterol, and to a lesser extent of the glycerides. DHA strongly inhibited the activity of glucose 6-phosphate dehydrogenase (d-glucose 6-phosphate: nicotinamide adenine dinucleotide phosphate oxidoreductase, EC 1.1.1.49) of this tissue. Although 6-phosphogluconate dehydrogenase (6-phospho-D-gluconate: N ADP oxidoreductase decarboxylating, EC 1.1.1.44) was not inhibited by DHA, the addition of 6-phosphogluconate did not reverse the inhibition of cholesterol synthesis. However, the addition of 6-phosphogluconate reversed the inhibition by DHA of glyceride synthesis. The results of this study do not support a primary causal relationship between the inhibition by DHA of glucose 6-phosphate dehydrogenase activity and of sterol synthesis. (Endocrinology 83: 1311, 1968)

New diphenylphosphane derivatives of ketoconazole are promising antifungal agents.

Abstract: Four new derivatives of ketoconazole (Ke) were synthesized: diphenylphosphane (KeP), and phosphane chalcogenides: oxide (KeOP), sulphide (KeSP) and selenide (KeSeP). These compounds proved to be promising antifungal compounds towards Saccharomyces cerevisiae and Candida albicans, especially in synergy with fluconazole. Simulations of docking to the cytochrome P450 14α-demethylase (azoles’ primary molecular target) proved that the new Ke derivatives are capable of inhibiting this enzyme by binding to the active site. Cytotoxicity towards hACSs (human adipose-derived stromal cells) of the individual compounds was studied and the IC50 values were higher than the MIC50 for C. albicans and S. cerevisiae. KeP and KeOP increased the level of the p21 gene transcript but did not change the level of p53 gene transcript, a major regulator of apoptosis, and decreased the mitochondrial membrane potential. Taken together, the results advocate that the new ketoconazole derivatives have a similar mechanism of action and block the lanosterol 14α-demethylase and thus inhibit the production of ergosterol in C. albicans membranes.