Avaliação da atividade antifúngica de amidas derivadas do ácido 3, 4, 5-trimetóxi-cinâmico frente a espécies de Candida

Abstract

In world biodiversity, is the genus Piper that has demonstrated a great abundance of metabolic with diverse biological activities. The following may be mentioned: lignans, neolignans, terpenes, propenylphenols, chalcones, flavones, benzenopyrans and especially amides. In this context, the substance piplartine, also known as piperlongumine, which is a trimethoxylated phenylpropanoid amide found in some species of the genus Piper, demonstrates different pharmacological activities, among them: antifungal, insecticide and repellent activities, leishmanicide, anxiolytic, antidepressive, potent inhibitor of platelet aggregation, and spasmolytic action in the rat aorta. Therefore, the present study aimed to prepare eight amides derived from 3,4,5-trimethoxy-cinnamic acid analogues of piplartine and to evaluate its antifungal potential, tracing a structure-activity relationship. Among the eight amides prepared in the present study, three amides presented activity against yeast strains of the genus Candida. Of these, two amides presented moderate activity with MIC values of 1024 μg/mL against strains of Candida albicans and Candida tropicalis. The third amide had optimal biological activity by presenting MIC of 256 μg/mL in most strains. N-(4-hydroxyphenethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide was the substance with the best biological activity against the tested strains. Comparative analysis of chemical structures of amides suggests that the presence of phenolic hydroxyl in N-(4-hydroxyphenethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide resulted in an increasement in fungicidal potency, being four times more potent for most of the strains. The data obtained in the present work can be used to advance the study of new antifungal prototypes. Keywords: Amides, piplartine, antifungal, Candida.