Terbinafine: Mode of action and properties of the squalene epoxidase inhibition

doi:10.1111/j.1365-2133.1992.tb00001.x

Paper

Terbinafine: Mode of action and properties of the squalene epoxidase inhibition

Published Feb 1, 1992 · N. Ryder

British Journal of Dermatology

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372

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17

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Abstract

Terbinafine (Lamisil®) has primary fungicidal action against many fungi as a result of its specific mechanism of squalene epoxidase inhibition. Treated fungi accumulate squalene while becoming deficient in ergosterol, an essential component of fungal cell membranes. The cidal action is closely associated with the development of high intracellular squalene concentrations, which are believed to interfere with fungal membrane function and cell wall synthesis. In the case of Candida albicans, growth inhibition with terbinafine appears to result from the ergosterol deficiency. The filamentous form of this fungus is more susceptible than the yeast form. Measurement of ergosterol biosynthesis by incorporation of radiolabelled precursors indicates a correlation between inhibition of growth and ergosterol biosynthesis in a range of pathogenic fungi. Terbinafine is a potent non‐competitive inhibitor of squalene epoxidase from Candida (Ki=30nm). In constrast, inhibition of rat liver squalene epoxidase only occurs at higher drug concentrations (Ki=77 μm), and is competitive with squalene. Thus, terbinafine has no effect on cholesterol biosynthesis in vivo. Squalene epoxidase is not an enzyme of the cytochrome P‐450 type, thereby avoiding potential inhibition of this class of enzymes.

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Study Snapshot

Terbinafine is a primary fungicidal agent against various fungi due to its specific mechanism of squalene epoxidase inhibition, causing fungal cell membrane dysfunction and cell wall synthesis.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Terbinafine: Mode of action and properties of the squalene epoxidase inhibition

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References

Biochemical mode of action and enantiomeric selectivity of SDZ 89-485, a new triazole antimycotic.

SDZ 89-485 effectively inhibits ergosterol biosynthesis in Candida, Trichophyton, and Aspergillus cells, with its (-)(R) enantiomer showing greater antifungal activity than its (+)(S) enantiomer.

Comparative effects of two antimycotic agents, ketoconazole and terbinafine on the metabolism of tolbutamide, ethinyloestradiol, cyclosporin and ethoxycoumarin by human liver microsomes in vitro.

Ketoconazole significantly inhibits tolbutamide, ethinyloestradiol, cyclosporin, and ethoxycoumarin metabolism in human liver microsomes, while terbinafine has less inhibitory effects.

The mechanism of action of terbinafine

Terbinafine's primary mechanism of action is the inhibition of squalene epoxidase, which is crucial for fungal ergosterol biosynthesis and its antimycotic properties.

Mechanism of Action and Biochemical Selectivity of Allylamine Antimycotic Agents

Allylamine antifungal agents, such as naftifine and terbinafine, effectively inhibit fungal ergosterol biosynthesis, providing high efficacy against dermatophytes and excellent tolerance in clinical use.

Synthesis and Structure‐ Activity Correlations within Allylamine Antimycotics

Naftifine and its derivative terbinafine are effective topical agents for treating skin mycoses, with terbinafine showing enhanced antifungal properties.

Antifungal activity of the allylamine derivative terbinafine in vitro

Terbinafine shows high antifungal activity against dermatophytes, aspergilli, and Sporothrix schenckii, as well as yeasts, with pH-dependent activity and varying effects on yeast species.

Inhibitory Effect of Antifungal Agents on Germ Tube Formation in Candida albicans. Hemmeffekt antifungaler Wirkstoffe auf die Keimschlauchbildung von Candida albicans

Clotrimazole, ketoconazole, and itraconazole are the most potent inhibitors of yeast-mycelial transformation in Candida albicans, with terbinafine showing a higher susceptibility than amphotericin B.

Inhibition of squalene epoxidase by allylamine antimycotic compounds. A comparative study of the fungal and mammalian enzymes.

Naftifine and compound SF 86-327 effectively inhibit squalene epoxidase in fungal yeasts, but show less sensitivity to rat liver enzymes, explaining their antimycotic action.

Citations

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Metabolic engineering in microbial cell factories, particularly yeasts, has shown promising progress in sustainable, environmentally friendly, and efficient production of squalene for various uses.

Evaluation of Fifteen 5,6-Dihydrotetrazolo[1,5-c]quinazolines Against Nakaseomyces glabrata: Integrating In Vitro Studies, Molecular Docking, QSAR, and In Silico Toxicity Assessments

Two new 5,6-dihydrotetrazolo[1,5-c]quinazoline derivatives show potent antifungal activity against Nakaseomyces glabrata, with potential for clinical use and minimal environmental and human toxicity.

Targeting squalene epoxidase in the treatment of metabolic-related diseases: current research and future directions

Targeting squalene epoxidase with inhibitors can effectively improve fungal infections, nonalcoholic fatty liver disease, and cancer.

Integrated Approach for Allyl Amine Synthesis Combining the Decarboxylative Coupling of Arylacrylic Acids with the Petasis Reaction.

This metal-free multicomponent reaction strategy efficiently synthesizes allyl amines without metal catalysts, achieving 78% yields across 30 diverse allyl amines.

The Kelch Repeat Protein VdKeR1 Is Essential for Development, Ergosterol Metabolism, and Virulence in Verticillium dahliae

VdKeR1 is essential for the growth, stress resistance, pathogenicity, and ergosterol metabolism of Verticillium dahliae, providing insights for potential control of Verticillium wilt.

Horizontal gene transfer-initiated reorganization of lipid metabolism drives lifestyle innovation in a eukaryote

Horizontal gene transfer in yeast allows for reorganization of lipid metabolism, allowing it to thrive in anoxia and adapt to new environments.