Benzoatos e benzamidas 3,4,5-trisubstituídas: Avaliação antifúngica e tripanocida

Abstract

Microbial and parasitic infections are a cause for concern worldwide because they are responsible for mortality and morbidity in a significant portion of the population, representing a serious threat to public health. Therefore, it is essential to search for new drug candidates for the treatment of these infections. Thus, in the present study, a collection of 20 synthetic analogues derived from gallic acid and 3,4,5-trimethoxybenzoic acid was prepared and a study was carried out against strains of the genus Candida and trypomastigote forms of Trypanosoma brucei. The Fischer and Schotten-Baumann esterification reactions were used to prepare the products, which were characterized by infrared spectroscopy, 1H NMR and 13C-APT. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and the possible antifungal action mechanism of the compound with the best biological activity. 4- methylbenzyl gallate (10) with MIC of 0.11 mM against C. albicans ATCC 60193 and MIC of 0.06 mM against C. tropicalis ATCC 750 was the derivative with the greatest antifungal potency. In the investigation of the mechanism of action, it was observed that compounds 7 and 10 interact directly with ergosterol present in the plasma membrane or in the fungal cell wall, which shows that these structures are possible biological targets. In the antiparasitic evaluation, compounds 1-8 were evaluated in the viability test of the human myeloid cell line (HL-60) through the resuzarin reduction method. In the trypanocidal assay, the blood trypomastigote forms of T. brucei were used to determine the MIC and IC50 of these compounds. In general, analogues 3, 5 and 7 demonstrated better trypanocidal action against T. brucei, suggesting that substituents with three and four carbon side chains in linear arrangement increase the antiparasitic potency of gallates. The data demonstrate the pharmacological potential of these chemical classes and that they can be used as prototypes in future research aiming at the development of products with better trypanocidal and antifungal profiles.