Synthesis and anti-Trypanosoma cruzi profile of the novel 4-thiazolidinone and 1,3-thiazole derivatives

Abstract

Chagas disease is a serious public health problem in Brazil and world. Caused by the protozoan Trypanosoma cruzi, it is estimated 6-7 million people infected worldwide. The only drug used to treatment is Benzonidazole, but this drug is only effective in the acute phase of the disease. This paper reports the synthesis and the anti-Trypanosoma cruzi activity of 4-thiazolidinone and 1,3-thiazole derivatives based in thiosemicarbazones previously described as potent trypanocidal agent, planned through the bioisosterism strategy. Therefore, the synthesis of 28 aryl-4-thiazolidinones (2a-r and 3a-j) was achieved, which aryl ring possesses halogens atoms in meta and para positions, and the heterocyclic system had lipophilic substituents. These compounds were thus evaluated as anti-T. cruzi agents against epimastigote, trypomastigote and amastigote forms of T. cruzi. Compounds were also tested its toxicity in L929 fibroblasts. In view to investigate a bioisosteric relationship between 1,3-thiazoles and 4-thiazolidinones, eighteen 1,3-thiazoles derived from trifluoromethyl thiosemicarbazone (4a-r) were also tested in the same model. It was possible to show that between the 46 tested compounds, those that possess a bromine (2a-r) atom showed better activity compared to compounds substituted by a trifluoromethyl group (3a-j) and to 1,3-thiazole derivatives (4a-r), which were inactive. In general, the 2a-r series showed low toxic profile in the cell line tested. Besides, compound 2h was the most active of then all when compared to the standard Benznidazole.