Synthesis of Hybrid Molecules with Imidazole-1,3,4-thiadiazole Core and Evaluation of Biological Activity on Trypanosoma cruzi and Leishmania donovani .

The aim of this work was to obtain and evaluate, as antiprotozoals, new derivatives of benzoate imidazo-1,3,4-thiadiazole 18 - 23 based on the concepts of molecular repositioning and hybridization. In the design of these compounds, two important pharmacophoric subunits of the fexnidazole prototype were used: metronidazole was used as a repositioning molecule, p-aminobenzoic acid was incorporated as a bridge group, and 1,3,4-thiadiazole group was incorporated as a second pharmacophore, which at position 5 has an aromatic group with different substituents incorporated. The final six compounds were obtained through a five-step linear route with moderate to good yields. The biological results demonstrated the potential of this new class of compounds, since three of them 19 - 21 showed inhibitory activity on proliferation, in the order of 50%, in the in vitro assay against epimastigotes of T. cruzi (Strain Y sensitive to nifurtimox and benznidazole) and promastigotes of L. donovani , at a single concentration of 50 μM.