Atividade antifúngica do cinamaldeído biossintético sobre Candida spp. de interesse clínico para cavidade bucal: estudo in silico e in vitro

Abstract

Background: One of the biggest challenges in the dental clinic is fungal infections resulting from the use of dental prostheses. This is due to the limited number of antifungal agents available on the market, as well as to increased microorganism resistance. Objective: This study aimed to evaluate the antifungal action of cinnamaldehyde against Candida species, its possible mechanisms of action in vitro, cytotoxicity against keratinocytes (HaCat), molecular interactions with enzymes related to formation of the fungal cell wall and membrane. Results: In molecular coupling simulations, the cinnamaldehyde-enzyme binding energy values showed that 4MAI (squalene epoxidase) presented the most stable interaction (-70.4951Kcal.mol-1), suggesting probable activity involving ergosterol biosynthesis. Six reference strains of Candida, (being sensitive and resistant to prescription antifungal agents), were used to determine Minimum Inhibitory Concentrations (MICs), Minimum Fungicide Concentrations (MFCs), possible mechanisms of action, and molecular docking. A descriptive and inferential statistical analysis was performed considering α (error type 1) = 5%. The MIC and MFC values ranged from 18.91μM to 37.83μM. The MIC values did not change in the presence of at the concentration of 0.8 M sorbitol, unlike what occurred in the presence of ergosterol, these values increased by 8 times. The action of Cinnamaldehyde likely includes binding to enzymes involved in formation of the cytoplasmic membrane of Candida genus fungi. Regarding the cytotoxicity tests, up to the concentration of 15μg / mL of cinnamaldehyde, 100% cell viability was observed, therefore, in fungicidal concentrations (5μg / mL), showed no cytotoxicity. Conclusions: Cinnamaldehyde showed fungicidal activity for the strains tested, with an ergosterol action mechanism, besides being non-cytotoxic with keratinocytes.