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3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile): A new highly active compound against epimastigote and trypomastigote form of Trypanosoma cruzi |
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| Authors: | Jana M Sandes Cláudio GL Junior Gabriel AU Carvalho Mário LAA Vasconcellos Regina CBQ Figueiredo |
| Institution: | a Departamento de Microbiologia, Centro de Pesquisas Aggeu Magalhães, FIOCRUZ, Recife, PE, Brazil b LASOM-PB, Departamento de Química, Universidade Federal da Paraíba, Campus I, 58059-900 João Pessoa, PB, Brazil c Laboratório de Química Quântica Computacional (LQQC)-Departamento de Química, Universidade Federal da Paraíba, Campus I, João Pessoa, PB 58059-900, Brazil |
| 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 IC50/72 h of 28.5 μM and also caused intense trypomastigotes lysis, with an IC50/24 h of 25.5 μM. 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. |
| Keywords: | Morita-Baylis-Hillman adducts Anti-Trypanosoma cruzi activity |
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