Studies toward the structural optimization of new brazilizone-related trypanocidal 1,3,4-thiadiazole-2-arylhydrazone derivatives

Megazol is a highly active compound against Trypanosoma cruzi, and has become a core structure for the design of new trypanocidal agents. Recently, we have identified the new potent trypanocide agent Brazilizone A, which presents an IC50 twofold more potent than the prototype megazol. This result has encouraged us to further explore structurally-related 1,3,4-thiadiazole-2-arylhydrazone derivatives, in order to get a better understanding of their structural and antiprotozoal activity relationships. Herein we report the synthesis and trypanocidal profile of thirteen new Brazilizone A analogues, which supported the construction of 3D-QSAR models used for its structural optimization.

We describe herein a 3D-QSAR model constructed with trypanocidal agents structurally-related to Brazilizone A (2) and the discovery of the 1,3,4-thiadiazole-2-arylhydrazone derivative (15), named Brazilizone N, as a novel potent antichagasic lead-candidate.Figure optionsDownload as PowerPoint slide