Avaliação antimicrobiana, citotóxica e de proteção solar in vitro e das propriedades farmacológicas e toxicológicas in silico da associação do ácido ferúlico e nicotinamida

Abstract

Ferulic acid is a potent natural antioxidant that can serve as a raw material for the development of new molecules and/or technological innovation of substances with known pharmacological activity. This study investigated the pharmacological and toxicological properties of ferulic acid (FA) and nicotinamide (NAM) and the combination of these substances. In silico assays were performed to predict the pharmacokinetic and toxicological properties of the substances, and in vitro tests were performed to determine: minimum inhibitory concentration (MIC), minimum bactericidal and fungicidal concentration (MBC/MFC), antifungal mechanism of action and microbial growth kinetics, hemolytic/antihemolytic effect and sun protection effect. The results demonstrated that FA and NAM have good pharmacokinetic parameters and ADMET profiles suitable for different therapeutic applications. FA showed low cytotoxic potential to human erythrocytes and a good sun protection effect, while for NAM, the protection factor was doseconcentration. The data from the antimicrobial tests showed that the isolated substances as associated agents had bactericidal and bacteriostatic effects on the Enterococus fecallis ATCC 29212 and Bacillus clausii O/C (CNCM-I276) strains. NAM and the synergistic combination of AF and NAM exhibited antifungal effects against C. albicans ATCC 60193. The synergistic combination of AF and NAM did not have its antifungal activity altered in the presence of ergosterol, however, in the presence of sorbitol, there was an increase in the MIC value. The synergistic combination of the test substances with nystatin did not show an antagonism effect. These findings open a new avenue for studies of the association of AF with NAM and possible combinations with reference antimicrobials and, relatively, with low cytotoxicity. Further investigations are needed to evaluate other mechanisms of action, including combinations with available drugs and long-term toxicity in other relevant models.