Compostos mesoiônicos: rearranjo molecular, atividade atioxidante e de inibição da Tirosinase

Abstract

This work involved the study of the 1,3,4-thiadiazolium-2-amine mesoionic compounds class rearrangement, in the corresponding 1,3,4-triazolium-2-thiolate and the chemo-biological properties evaluation, such as antioxidant and antitirosinase activities. The mesoionic compounds generally possess structures which allow new heterocycles synthesis, and also interactions with biomolecules, such as DNA and proteins, which are important factors to explain their different biological activities. The mesoionic compounds studied in this work were the 1,3,4-triazolium-2-thiolate class obtained by the molecular rearrangement of their 1,3,4-thiadiazole-2-amine isomers in the presence of the nucleophilic solvents, under reflux and microwave irradiation. The 1,2,3- oxadiazolium-5-olate (sydnones) class were further synthesized. Mesoionic derivatives of the 1,3,4-thiadiazolium-2-aminide class, in hydrochloride form as well as a free base, and the 1,2,3-oxadiazolium-5-olate class were obtained by classical reactions already described in the literature. The use of microwave irradiation, in the presence of solid support and the Lewis acid, provided the mesoionic compounds 1,3,4-triazolium-2-tiolate in unprecedented quantitative yields, and much smaller reaction times (3 minutes) when compared to traditional methods (8 hours). Therefore, it presented high efficiency in molecular rearrangement. All synthesized mesoionic compounds were characterized by spectroscopic techniques, such as IR, UV, 1H and 13C NMR. The antioxidant activity evaluation of the mesoionic compounds showed to be promising for the 1,3,4-triazolium-2-thiolate and 1,3,4-thiadiazole-2-amine classes, especially in the hydrochloride form. The evaluation of the tyrosinase enzyme inhibition was performed to all synthesized compounds, but a higher activity was noticed in the 1,2,3-oxadiazole-5-olate class derivatives results.