Aryl- or heteroaryl-based hydrazinylphthalazine derivatives as new potential antitrypanosomal agents.

Angel H Romero, Jonathan Rodríguez, Yael García-Marchan, Jacques Leañez, Xenón Serrano-Martín, Simón E López

Bioorganic chemistry 2017 Jun

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A series of twenty phthalazinyl-hydrazones were synthesized and tested as potential anti-Trypanosoma cruzi agents. The phthalazines containing 5-nitroheteroaryl moiety 3l and 3m displayed an excellent in vitro antitrypanosomal profile, exhibiting low micromolar EC50 values against proliferative epimastigote of T. cruzi and minimal toxicity toward Vero cells. These derivatives were more potent than the reference drug benznidazole against the epimastigote stage of the parasite. Structure-property analysis indicates that the highly conjugated 5-nitroheteroaryl moiety connected to the phthalazin scaffold play an important role in the antichagasic activity of these phthalazines. The decrease on the mitochondrial dehydrogenase activity and significant ROS production found for the parasites treated with 3l and 3m suggest that both nitro-derivatives can act through an oxidative stress mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

Citation

Angel H Romero, Jonathan Rodríguez, Yael García-Marchan, Jacques Leañez, Xenón Serrano-Martín, Simón E López. Aryl- or heteroaryl-based hydrazinylphthalazine derivatives as new potential antitrypanosomal agents. Bioorganic chemistry. 2017 Jun;72:51-56