Atividade antifúngica do 2-benzil-5-metilbenzo[d]xazol frente a candida spp.

Abstract

Over the past three decades, there has been a significant increase in the incidence of fungal infections caused by Candida species. Among these, oral candidiasis stands out as the most common oral fungal infection, primarily triggered by Candida albicans. Vulnerable groups include cancer patients, immunosuppressed individuals, and denture users. However, current treatments are associated with adverse effects and increasing pathogen resistance, making it urgent to search for new, more effective, and safer pharmacological compounds for treating these infections. This study aimed to evaluate the antifungal potential of 2-benzyl-5-methylbenzo[d]oxazole (Compound 1), a benzoxazole derivative, against Candida species. The antifungal activity was determined using the broth microdilution technique to establish the minimum inhibitory concentration (MIC). Subsequently, agar plates containing SDA were used to determine the minimum fungicidal concentration (MFC). Additionally, the compound's effects on biofilm formation were assessed, focusing on both the adhesion phase and mature biofilm. Tests with sorbitol and ergosterol were conducted to investigate the action of Compound 1 on the fungal cell wall and membrane, respectively. An in silico analysis of pharmacokinetic and toxicological properties was performed using ADMET, Molinspiration, and Passonline software. The MIC values varied across species: MIC of 16 µg/mL for C. krusei, MIC of 32 µg/mL for C. albicans and C. parapsilosis, and MIC of 64 µg/mL for C. glabrata. The MFC/MIC ratio < 4 indicated fungicidal activity, and the probable mode of action involves the plasma membrane, as an increase in MIC was observed in the presence of exogenous ergosterol. A 64% reduction in pre- formed biofilm and 84% inhibition of biofilm in the adhesion phase were observed, both at a concentration of 320 µg/mL (p < 0.0001). In in silico tests, 2-benzyl-5- methylbenzo[d]oxazole exhibited good theoretical bioavailability after oral administration, good solubility, stability, and absorption, along with moderate theoretical toxicity. Based on these findings, 2-benzyl-5-methylbenzo[d]oxazole demonstrated promising pharmacological activity. These results may serve as an important starting point for developing new antifungal drug candidates, although further studies are required to evaluate its cytotoxicity.