Atividade antifúngica e antibiofilme de derivados triazólicos de eugenol e timol frente a Candida spp

Abstract

Fungal infections, mainly caused by species of the genus Candida, represent a growing global health problem. Available treatment is limited, with emphasis on azoles, widely used due to their broad spectrum, efficacy, and safety. However, the development of antifungal resistance has compromised their efficacy, highlighting the need for new molecules. This study evaluated the antifungal activity of 09 triazole compounds derived from eugenol and 19 derivatives of thymol against Candida albicans and non-albicans Candida spp. The results demonstrated that the eugenol-derived compounds 3a, 3e and 3i, and the thymol derivative 3g, have significant antifungal action, with antibiofilm activity, acting on the permeability, cell wall and ergosterols of the cell membrane of several Candida species. 3e presented more homogeneous MIC and MFC values among the species tested, ranging from 125 to 250 ppm, and presented relevant values in biofilm inhibition, especially against Pichia kudriavzevii (Candida krusei) and Nakaseomyces glabratus (Candida glabrata). In the disarticulation of mature biofilms, it demonstrated significant results for C. albicans. It also promoted substantial changes in the integrity of the cell membrane, particularly in P. kudriavzevii (C. krusei) and Candida tropicalis. The triazole derivative 3g demonstrated superior antifungal and antibiofilm activity to pure thymol against Candida species, including N. glabratus (C. glabrata), C. albicans and Candida parapsilosis. MIC and MFC tests revealed its inhibitory efficacy, while membrane permeability and ergosterol synthesis assays confirmed its mechanism of action, which compromises the structural integrity of fungal cells. Furthermore, 3g was effective both in preventing biofilm formation and in disrupting mature biofilms. Among the compounds evaluated, 3e and 3g demonstrated multiple mechanisms of action, which highlights promising characteristics for the development of new antifungal agents. In vivo studies are needed to validate the clinical use and evaluate the safety and effectiveness of the compounds.