In vitro susceptibility of fungi to acyclic inhibitors of 2,3-oxidosqualene cyclases

• Published in: Mycoses Vol. 39; no. 1-2; pp. 51 - 56
• Main Authors: Airaudi, D., Ceruti, M., Bianco, C., Marchisio, V. Filipello
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.1996; Blackwell
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - pharmacology; Aspergillus; Biological and medical sciences; Enzyme Inhibitors - pharmacology; Epidermophyton; Epidermophyton - drug effects; Epidermophyton floccosum; Fungi - drug effects; Fungi - isolation & purification; fungitoxicity; Humans; Intramolecular Transferases; Isomerases - antagonists & inhibitors; Medical sciences; Microbial Sensitivity Tests; Microsporum; Microsporum - drug effects; Microsporum canis; Mitosporic Fungi - drug effects; Pharmacology. Drug treatments; Scopulariopsis; Squalene - analogs & derivatives; Squalene - pharmacology; squalenoid derivatives; sterol biosynthesis; Structure-Activity Relationship; Trichophyton; Trichophyton - drug effects; Trichophyton mentagrophytes; Trichophyton terrestre; Infection; Human; Antifungal agent; Sensitivity; Treatment; Mycosis; Minimum inhibitory concentration; Squalene; Drift; Inhibitor; In vitro
• ISSN: 0933-7407; 1439-0507
• DOI: 10.1111/j.1439-0507.1996.tb00084.x

In the present study we determine the antifungal properties of two acyclic inhibitors of 2,3‐oxidosqualene cyclases: 22,23‐epoxy‐2‐aza‐2,3‐dihydrosqualene (EAS) and azasqualene alcohol (ASA). Fungistatic and fungicidal activity towards dermatophytes and other fungi involved in cutaneous and systemic infections was tested (48 isolates from 10 species). The tests were carried out by inoculating 10 μl of mycelial homogenate in 1 ml of Sabouraud glucose liquid medium containing serial dilutions of 100 to 0.25 μg ml‐1 of the substance. For each isolate, the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) of both compounds were determined. EAS was more active (MIC range 1.5–25 μg ml‐1) than ASA (MIC range 3–50 μg ml‐1). At the highest concentration tested, EAS also showed fungicidal action towards some isolates of Trichophyton mentagrophytes, T. terrestre, Epidermophyton floccosum, Microsporum canis and Scopulariopsis brumptii. The most sensitive species was T. mentagrophytes, the most resistant T. rubrum. Zusammenfassung. In der vorliegenden Studie wurden die antifungalen Eigenschaften zweier azyklischer 2,3‐Oxidosqualcncyclase‐Hemmer untersucht, nämlich des 22,23‐Epoxy‐2‐aza‐2,3‐dihydrosqualens (EAS) und des Azasqualen‐alkohols (ASA). Die fungistatische Aktivität wurde an Dermatophyten und anderen Mykose‐Erregern untersucht (48 Isolate von 10 Arten). Methodisch wurden Reihenverdünnungsteste mit je 10μl Myzelhomogenat in je 1 ml Sabouraud‐Glucose‐Bouillon im Bereich von 100–0.25 μg ml‐1 der Testsubstanzen eingesetzt. Für jedes Isolat wurden die minimale Hemmkonzentration (MIC) und die minimale fungizide Konzentration (MFC) beider Substanzen bestimmt. EAS (MIC‐Bereich 1.5–25 μg ml‐1) war stärker aktiv als ASA (MIC‐Bereich 3–50 μ ml‐1). In der höchsten geprüften Konzentration war EAS fungizid für einige Isolate von Trichophyton mentagrophytes, T. terrestre, Epidermophyton floccosum, Microsporum canis und Sccpulariopsis brumptii. Die empfindlichste Species war T. mentagrophytes, die resistenteste T. rubrum.