Síntese e avaliação da atividade antitripanossoma de análogos 3-nitro-1,2,4-triazóis isoxazólicos

Abstract

Neglected tropical diseases (NTDs) are a group of infectious diseases that primarily affect underdeveloped countries. Due to the lack of expected financial return, they often receive little attention from the pharmaceutical industry. Chagas disease is a neglected disease caused by the Trypanosoma cruzi parasite. It is estimated that over 6 million people worldwide are affected by the disease, with a large portion remaining asymptomatic. The treatment has limitations, such as a high incidence of side effects, ineffectiveness in chronic-phase patients, and in recent years, the emergence of drug-resistant strains. Thus, new drug candidates need to be developed for the treatment of this disease. Heterocyclic derivatives have emerged as an alternative in the design of new drug candidates. Nitrotriazoles and isoxazoles have been widely used in the discovery of new trypanosomatid bioactive compounds through molecular modification strategies such as bioisosterism. Therefore, given the problems presented in relation to Chagas disease and limited pharmacological treatment, thos work aimed to syntethsize na unprecedented class oof new heterocyclic derivatives, Where four 3-nitro-1,2,4-triazole-isoxazole derivatives with different substitution patterns were synthesized, achieving yields ranging from 53% to 68%, which were evaluated and demonstrated potential antitrypanosomal, since they presented better results (IC50 = 2.32 µM) than those of Benznidazole (IC50 = 5.10 µM),.