2-Pyridyl thiazoles as novel anti-Trypanosoma cruzi agents: Structural design, synthesis and pharmacological evaluation

• 20 compounds showed good inhibition levels on the trypomastigote form of the parasite.
• 9 compounds inhibited cruzain enzyme with IC50 0.01–9.5 μM.
• None of the compounds tested shown cytotoxicity.
• The hybridization of 2-pyridine and 1,3-thiazole achieved potent trypanocidal activity.
• Docking studies corroborated with binding results on cruzain.

The present work reports on the synthesis, anti-Trypanosoma cruzi activities and docking studies of a novel series of 2-(pyridin-2-yl)-1,3-thiazoles derived from 2-pyridine thiosemicarbazone. The majority of these compounds are potent cruzain inhibitors and showed excellent inhibition on the trypomastigote form of the parasite, and the resulting structure–activity relationships are discussed. Together, these data present a novel series of thiazolyl hydrazones with potential effects against Chagas disease and they could be important leads in continuing development against Chagas disease.

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