Эбурикол

Description

Eburicol (24-methylene-24,25-dihydrolanosterol) is a natural mushroom sterol, an intermediate product of ergosterol biosynthesis.

Basic Attributes

• CAS No.: 6890-88-6
• Chemical formula: C31H52O
• Molecular weight: 440.74398
• Exact weight: 440.74
• PSA specifications: 20.2 Ų

Physico-chemical characteristics

• Melting point: 158–159 °C

Role in ergosterol biosynthesis

Eburicol is demethylated by the yeast cytochrome P450-dependent sterol 14 alpha demethylase ERG11 (eburicol 14 alpha demethylase, CYP51), a key enzyme in the biosynthesis of ergosterol. In Aspergillus fumigatus, eburicol is the preferred substrate of the Erg11 orthologs, the enzymes Cyp51A and Cyp51B; Eburicol itself is formed from lanosterol under the action of the Erg6 enzyme. Erg6 catalyzes SAM-dependent methyl addition at C-24 with a double bond shift, forming a C-24(28)-methylene structure.

Clinical significance

Mutations in the CYP51 gene, which encodes the target of azole antifungals, are associated with decreased effectiveness of some azole fungicides; analysis of concomitant sterols, particularly the accumulation of the CYP51 substrate eburicol, is used as an indicator of azole resistance.

Substance class

Tetracyclic triterpenoid sterol of the lanostane series. The low PSA value (20.2 Ų) is typical for sterol structures with a single hydroxyl group and explains the high lipophilicity and membrane localization of the compound in the fungal cell.

Scope of application

Research reagent and analytical standard for studying ergosterol biosynthesis and mechanisms of fungal resistance to azole antimycotics.

Significance of the ergosterol biosynthesis pathway

Ergosterol is a functional analogue of cholesterol in fungal membranes, providing the necessary fluidity and permeability of the lipid bilayer; its absence in mammals is the basis for the selectivity of all azole and polyene antimycotics. The pathway from lanosterol to ergosterol involves more than a dozen enzymatic steps, and eburicol is one of the key intermediates precisely at the site catalyzed by the azole target CYP51/ERG11. Understanding which specific sterol intermediate accumulates when the enzyme is blocked allows us to distinguish between strains with different types of resistance mutations based on the profile of sterol accumulation and evaluate the effectiveness of new chemical structures being developed to bypass resistance to existing antifungal drugs.

Clinical relevance of resistance

Resistance of Aspergillus fumigatus to azole antimycotics is considered one of the most significant problems of modern clinical mycology, since azoles are the main class of drugs for the treatment of invasive aspergillosis. Resistant strains are increasingly being isolated from clinical material from patients previously treated with azole therapy, as well as from environmental objects, which is associated with the widespread agricultural use of azole fungicides that act on the same molecular mechanism. In this context, the study of sterol intermediates in the ergosterol biosynthetic pathway, including eburicol, remains one of the key laboratory approaches to understanding the molecular nature of acquired resistance.