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.

Identification of an indole–triazole–amino acid conjugate as a highly effective antifungal agent

Abstract: Compounds constructed by the grafting of amino acid and triazole with an indole moiety were synthesized and investigated for antifungal activities wherein one of the compounds gave highly promising results. Although the compound has a high MIC80 value in liquid medium, it shows significant antifungal activity against Candida albicans in solid plate assays. The compound is found to target chitin in the cell wall and lanosterol 14α-demethylase of the ergosterol biosynthesis pathway. The inhibitory effect of the compound becomes more pronounced in combination with azoles and CFW. The compound is also found to significantly affect chitin levels, cell morphology and cell viability in combination with ketoconazole.

Synthesis of Lanosterol Analogs with Modified Side Chains

Abstract: Starting from lanosteryl acetate (1b), we synthesized twelve lanosterol analogs (cf. Chart 1-3 ; 9, 11, 14, 16, 18a, 19, 26, 27a, 28, 29, 30, 32) with different sizes of side chain and 20-iso-24-dihydrolanosterol (37), for biological studies. The analogs have shorter side chains than 1b except for the 24-ethylidene derivative (19) and 37. 20-Iso-24-di-hydrolanosterol (37) was prepared via 20-iso-22-dehydro-24-dihydrolanosterol [obtained by the Wittig reaction of 20R, S-aldehyde mixture (6, 33) with isoamyl triphenylphosphonium iodide, followed by column chromatographic separation].

Cholesterol Biosynthesis from Lanosterol: Development of a Novel Assay Method, Characterization, and Solubilization of Rat Hepatic Microsomal Sterol Δ 7 -Reductase

Abstract: A novel assay method is described for rapid quantitation of reaction rate of sterol -reductase (-SR) which catalyzes reduction of the -double bond of sterols. Of six different organ tissues-liver, small intestine, brain, lung, kidney, and testis-. -SR activity was detected only in liver (2.30 nmol/min/mg protein) and testis (0.11 nmol/min/mg protein). Using a newly developed method which employs diet-induced enzyme proteins and ergosterol as substrate, we assessed both kinetics (, ) and inhibition of the rat hepatic -SR against well-studied cholesterol lowering agents such as triparanol (). 3--[2-(diethylamino)ethoxy]androst-5-en-17-one (U18666A) (), and trans-1.4-bis(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride (AY-9944) (). Of the three well-known AY-9944-sensitive cholesterogenic enzymes (i.e., -SR, sterol -isomerase, and sterol -reductase). -SR was found to be the most sensitive enzyme with a noncompetitive inhibition of this compound (). Substrate specificity studies of the microsomal -SR indicate that the relative reaction rate for 7-dehydrocholesterol and ergosterol are 5.6-fold and 1.6-fold higher than that for lathosterol. -SR activity was also modulated by feeding rats a diet supplemented with 0.5% ergosterol (>2.6-fold) in addition to 5.0% cholestyramine plus 0.1% lovastatin (5.0-fold). Finally, microsomal -SR was solubilized by 1.5% 3-[3-(cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) and enriched on PEG (0~10%) precipitation, which should be suitable for further purification of the enzyme.

Biochemical model of action and enantiomeric selectivity of SDZ 89–485, a new triazole antimycotic

Abstract: SDZ 89-485, a new triazole antimycotic agent, potently inhibited ergosterol biosynthesis in cells of Candida, Trichophyton and Aspergillus. Biosynthesis was measured both by incorporation of radiolabelled acetate and also by methylation of the sterol side chain. Inhibition was accompanied by accumulation of radiolabel in 4,4-dimethylsterols and to a lesser extent in the 4-methylsterols, consistent with inhibition of lanosterol 14-demethylation. No other steps were affected. Ergosterol biosynthesis in the mycelial growth form of Candida albicans was about twice as sensitive to the drug as that in the yeast form. Inhibition by SDZ 89-485 was qualitatively and quantitatively similar to that shown by other systemically active azoles (ketoconazole, itraconazole, ICI 195,739) in Candida cells and cell-free preparations. Rat liver cell-free cholesterol biosynthesis was much less sensitive to inhibition by SDZ 89-485 than was the equivalent Candida system (selectivity ratio of about 300). In contrast to miconazol...