3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile): A new highly active compound against epimastigote and trypomastigote form of Trypanosoma cruzi

Bioorganic Chemistry
Jana M SandesRegina C B Q Figueiredo

Abstract

We have synthesized the Morita-Baylis-Hillman adduct (MBHA) 3-hydroxy-2-methylene-3-(4-nitrophenyl)-propanenitrile (3) in quantitative yield and evaluated on Trypanosoma cruzi epimastigote and bloodstream trypomastigote forms. Compound 3 strongly inhibited epimastigote growth, with IC(50)/72hof 28.5 microM and also caused intense trypomastigotes lysis, with an IC(50)/24h of 25.5 microM. Ultrastructural analysis showed significant morphological changes on both parasite forms treated with 3, including increase of cell volume and rounding of cell body as well as intense intracellular disorganization. Morphological changes indicative of apoptosis, autophagy or necrosis were observed in most affected cells. Docking calculations of 1, 2 and 3 pointed out the possibility of T. cruzi Farnesyl Pyrophosphate Synthase (TcFPPS) enzyme inhibition in 3 mechanism of action.

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Citations

Dec 30, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Júlio César L MenezesJason G Taylor
Apr 9, 2013·Toxicon : Official Journal of the International Society on Toxinology·Camila M AdadeThaïs Souto-Padrón
Oct 3, 2012·Parasitology·Camila M AdadeThaïs Souto-Padrón

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