Planejamento sintético, atividade antimicrobiana e toxicológica de um híbrido ftalimídico triazólico.

Abstract

The 1,2,3-1H-triazole compounds are extremely important heterocyclic compounds, due to their stability, low toxicity and several synthetic, technological and pharmacological applications, highlighting their notorious antimicrobial property in the fight against new infectious diseases that affect society, mainly due to the emergence of resistant microorganisms. In parallel, a Phthalimide group can be introduced to the compound 1,2,3-1H-triazoles, which is a cyclic imide that has numerous pharmacological properties, which may result in the potentiation of antimicrobial activity. However, even in the face of such groups acting as antimicrobials, it is initially essential to carry out a toxicological test to predict possible undesirable effects. Therefore, the present research aimed to develop a study of the reaction conditions to obtain a phthalimidic-triazole hybrid, to characterize it through spectrometric techniques and to evaluate its antimicrobial activity and, additionally, to carry out the toxicological bioassay of this hybrid against the larvae. of Artemia salina. N-(4azidobutyl)phthalimide was obtained from the bimolecular nucleophilic substitution reaction under argon atmosphere, in the form of a white solid with a yield of 85% and, once synthesized, this phthalimidic azide was used for the synthesis of phthalimidic-triazole hybrid according to the technique described by Sharpless and Mendal in 2002 the CuAAC reaction; was characterized and used in the study of the reaction conditions for the synthesis of the phthalimidic-triazole hybrid. The results showed that solvents with intermediate polarity favored the protocol, but the yield using water:n-propanol was higher compared to other hydroalcoholic systems. In addition, the basic species that promoted the most efficient results was potassium carbonate, justified by Pearson's acid-base theory, at room temperature and using ultrasonic energy due to acoustic cavitation processes. Once the reaction conditions of the phthalimidic-triazole hybrid were optimized, it was submitted to the toxicological assay, which showed moderate toxicity with a LC50 of 100.68 ppm, and antifungal activity with equivalent MIC values of 64 µg/mL and 128 µg/ mL for Candida albicans and Candida tropicalis, respectively. In short, the new phthalimidic-triazole hybrid developed presents itself as a potential therapeutic agent given the exhaustion of therapeutic actions promoted by antimicrobial resistance.