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

被引：24

作者：

Sandes, Jana M. ^{[1
]}

Borges, Andrezza R. ^{[1
]}

Junior, Claudio G. L. ^{[2
]}

Silva, Fabio P. L. ^{[2
]}

Carvalho, Gabriel A. U. ^{[3
]}

Rocha, Gerd B. ^{[3
]}

Vasconcellos, Mario L. A. A. ^{[2
]}

Figueiredo, Regina C. B. Q. ^{[1
]}

机构：

[1] Fiocruz MS, Dept Microbiol, Ctr Pesquisas Aggeu Magalhaes, Recife, PE, Brazil

[2] Univ Fed Paraiba, LASOM PB, Dept Quim, BR-58059900 Joao Pessoa, Paraiba, Brazil

[3] Univ Fed Paraiba, LQQC, Dept Quim, BR-58059900 Joao Pessoa, Paraiba, Brazil

来源：

BIOORGANIC CHEMISTRY | 2010年 / 38卷 / 4-6期

关键词：

Morita-Baylis-Hillman adducts; Anti-Trypanosoma cruzi activity; BAYLIS-HILLMAN REACTION; FARNESYL DIPHOSPHATE SYNTHASE; ADDUCTS; DISEASE; ACID; BENZNIDAZOLE;

D O I：

10.1016/j.bioorg.2010.06.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 mu M and also caused intense trypomastigotes lysis, with an IC50/24 h of 25.5 mu M. 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 (TcFPFS) enzyme inhibition in 3 mechanism of action. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：190 / 195

页数：6

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