title: 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile): A new highly active compound against epimastigote and trypomastigote form of Trypanosoma cruzi.
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.
authors.affiliation: Departamento de Microbiologia, Centro de Pesquisas Aggeu Magalhães, FIOCRUZ, Recife, PE, Brazil.
authors.forename: Jana M
authors.initials: JM
authors.lastname: Sandes
authors.forename: Andrezza R
authors.initials: AR
authors.lastname: Borges
authors.forename: Cláudio G L
authors.initials: CG
authors.lastname: Junior
authors.forename: Fábio P L
authors.initials: FP
authors.lastname: Silva
authors.forename: Gabriel A U
authors.initials: GA
authors.lastname: Carvalho
authors.forename: Gerd B
authors.initials: GB
authors.lastname: Rocha
authors.forename: Mário L A A
authors.initials: ML
authors.lastname: Vasconcellos
authors.forename: Regina C B Q
authors.initials: RC
authors.lastname: Figueiredo
mesh_terms: D000181:Acrylonitrile / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001592:Benzyl Alcohols / Q000138:chemical synthesis* / Q000494:pharmacology*; D014355:Chagas Disease / Q000188:drug therapy*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D009570:Nitriles; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
chemical_list: C510493:3-hydroxy-2-methylene-3-(4-nitrophenyl)propanenitrile; D001592:Benzyl Alcohols; D009570:Nitriles; D014344:Trypanocidal Agents; D000181:Acrylonitrile