Design e síntese de novos derivados 2-nitrotriazol acilhidrazona com potencial atividade antitripanossoma

Abstract

American trypanosomiasis, or Chagas disease, is a neglected tropical disease that affects, primarily, Latin America. Caused by the protozoan parasite Trypanosoma cruzi, it is estimated that over 10,000 deaths occur annually due to the clinical manifestations of the disease. Additionally, approximately 100 million people are considered vulnerable and at risk of acquiring the infection. The two drugs currently approved for Chagas disease treatment, benznidazole and nifurtimox, are associated with significant adverse effects such as itching, skin rash, sensory neuropathy, dyspnea, and nausea, factors that contribute to poor treatment adherence and frequent discontinuation. Moreover, the efficacy of both drugs is drastically reduced in the later stages of infection. In this context, the search for new compounds with antitrypanosomal activity is urgent. Thus, nitroheterocyclic compounds stand out as a class with great anti-T. cruzi potential, especially when combined with the acylhydrazone group. Therefore, the present project synthesized six new 2-nitrotriazole acylhydrazone derivatives, using molecular bioisosterism as a medicinal chemistry strategy. The methodology involved a four-step synthetic route: synthesis of 2-nitrotriazole, conversion to the corresponding ester, reaction with hydrazine to form acetohydrazide, and subsequent condensation with differently substituted benzaldehydes, and then, the obtained molecular structures were confirmed using Hydrogen (¹H) and Carbon (13C) Nuclear Magnetic Resonance (NMR) spectroscopy. In the future, the new compounds will undergo anti-T. cruzi activity tests, thus contributing to the development of promising candidates for the treatment of Chagas disease and exploring bioactive scaffolds that are poorly studied and have potential antitrypanosomal.