Evaluation of (-)-Fenchone antimicrobial activity against oral Candida albicans and toxicological parameters: an in silico, in vitro and ex vivo study

• Published in: Anais da Academia Brasileira de Ciências Vol. 96; no. 4; p. e20240273
• Main Authors: SANTOS, ANDRÉ A. DOS, OLIVEIRA-FILHO, ABRAHÃO A. DE, TEIXEIRA, BRÁULIO A., GALVÃO, JOSÉ LUCAS F.M., MEDEIROS, MARIA ALICE A. DE, ALVES, MILLENA S., BARBOSA, DAVID HENRIQUE X., MAFRA, RODRIGO P., VASCONCELOS, ULRICH, LIMA, EDELTRUDES O.
• Format: Journal Article
• Language: English
• Published: 2024
• ISSN: 0001-3765; 1678-2690; 1678-2690
• DOI: 10.1590/0001-3765202420240273

Candida albicans is the primary species causing oral candidiasis. Its increasing drug resistance drives the search for more effective antifungal agents. Therefore, we assessed toxicological parameters and the antimicrobial activity and mechanisms of action of the monoterpene (-)-fenchone against oral C. albicans. We conducted an in silico study using PASS online and AdmetSAR, followed by evaluation of antifungal activity through Minimum Inhibitory Concentration (MIC), Minimum Fungicidal Concentration (MFC), association study with miconazole, and assays with sorbitol and ergosterol. Inhibition of biofilm formation and disruption of preformed biofilm were considered. Toxicity was also assessed through hemolysis assay. The in silico study revealed a higher likelihood of the compound being active for antifungal activity, as well as promising pharmacokinetic and toxicity characteristics. Subsequently, (-)-fenchone exhibited predominantly fungicidal activity (MIC90 = 8 μg/mL; MFC = 16 μg/mL), including against miconazole-resistant C. albicans isolates. The substance does not appear to act by damaging the fungal cell wall or plasma membrane, and exhibited synergy with miconazole. There was activity in inhibiting biofilm formation but not in disrupting preformed biofilm. Finally, the product exerted low hemolytic activity at more than MIC×10. Based on these results, (-)-fenchone may represent a promising therapeutic alternative for oral candidiasis.Candida albicans is the primary species causing oral candidiasis. Its increasing drug resistance drives the search for more effective antifungal agents. Therefore, we assessed toxicological parameters and the antimicrobial activity and mechanisms of action of the monoterpene (-)-fenchone against oral C. albicans. We conducted an in silico study using PASS online and AdmetSAR, followed by evaluation of antifungal activity through Minimum Inhibitory Concentration (MIC), Minimum Fungicidal Concentration (MFC), association study with miconazole, and assays with sorbitol and ergosterol. Inhibition of biofilm formation and disruption of preformed biofilm were considered. Toxicity was also assessed through hemolysis assay. The in silico study revealed a higher likelihood of the compound being active for antifungal activity, as well as promising pharmacokinetic and toxicity characteristics. Subsequently, (-)-fenchone exhibited predominantly fungicidal activity (MIC90 = 8 μg/mL; MFC = 16 μg/mL), including against miconazole-resistant C. albicans isolates. The substance does not appear to act by damaging the fungal cell wall or plasma membrane, and exhibited synergy with miconazole. There was activity in inhibiting biofilm formation but not in disrupting preformed biofilm. Finally, the product exerted low hemolytic activity at more than MIC×10. Based on these results, (-)-fenchone may represent a promising therapeutic alternative for oral candidiasis.