Rational design of nitrofuran derivatives: Synthesis and valuation as inhibitors of Trypanosoma cruzi trypanothione reductase

2017 ◽  
Vol 125 ◽  
pp. 1088-1097 ◽  
Author(s):  
D.G. Arias ◽  
F.E. Herrera ◽  
A.S. Garay ◽  
D. Rodrigues ◽  
P.S. Forastieri ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Rational Design ◽  
Trypanothione Reductase ◽  
Nitrofuran Derivatives

scholarly journals KBE009: A Bestatin-Like Inhibitor of the Trypanosoma cruzi Acidic M17 Aminopeptidase With In Vitro Anti-Trypanosomal Activity

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1037
Author(s):  
Jorge González-Bacerio ◽  
Irina Arocha ◽  
Mirtha Elisa Aguado ◽  
Yanira Méndez ◽  
Sabrina Marsiccobetre ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Rational Design ◽  
Specific Effect ◽  
Dermal Fibroblasts ◽  
Aminopeptidase Activity ◽  
Geometrical Shape ◽  
Starting Point ◽  
Insight Into ◽  
Leucyl Aminopeptidase

Chagas disease, caused by the kinetoplastid parasite Trypanosoma cruzi, is a human tropical illness mainly present in Latin America. The therapies available against this disease are far from ideal. Proteases from pathogenic protozoan have been considered as good drug target candidates. T. cruzi acidic M17 leucyl-aminopeptidase (TcLAP) mediates the major parasite’s leucyl-aminopeptidase activity and is expressed in all parasite stages. Here, we report the inhibition of TcLAP (IC50 = 66.0 ± 13.5 µM) by the bestatin-like peptidomimetic KBE009. This molecule also inhibited the proliferation of T. cruzi epimastigotes in vitro (EC50 = 28.1 ± 1.9 µM) and showed selectivity for the parasite over human dermal fibroblasts (selectivity index: 4.9). Further insight into the specific effect of KBE009 on T. cruzi was provided by docking simulation using the crystal structure of TcLAP and a modeled human orthologous, hLAP3. The TcLAP-KBE009 complex is more stable than its hLAP3 counterpart. KBE009 adopted a better geometrical shape to fit into the active site of TcLAP than that of hLAP3. The drug-likeness and lead-likeness in silico parameters of KBE009 are satisfactory. Altogether, our results provide an initial insight into KBE009 as a promising starting point compound for the rational design of drugs through further optimization.

ChemInform Abstract: Structure-Activity Relationships in 2-Aminodiphenylsulfides Against Trypanothione Reductase from Trypanosoma cruzi.

ChemInform ◽  
2010 ◽  
Vol 29 (38) ◽  
pp. no-no
Author(s):  
S. GIRAULT ◽  
E. DAVIOUD-CHARVET ◽  
L. SALMON ◽  
A. BERECIBAR ◽  
M.-A. DEBREU ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Trypanothione Reductase ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Abstract Structure

Trypanosoma cruzi: effect and mode of action of nitroimidazole and nitrofuran derivatives

2003 ◽  
Vol 65 (6) ◽  
pp. 999-1006 ◽  
Author(s):  
Juan Diego Maya ◽  
Soledad Bollo ◽  
Luis J. Nuñez-Vergara ◽  
Juan A. Squella ◽  
Yolanda Repetto ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Mode Of Action ◽  
Nitrofuran Derivatives

1,3-Disubstituted-5-nitroindazole derivatives are inhibitors and subversive substrates of trypanothione reductase from Trypanosoma cruzi

2013 ◽  
Vol 65 ◽  
pp. S23
Author(s):  
B. Aguilera-Venegas ◽  
C. Olea-Azar ◽  
H. Speisky ◽  
V.J. Arán ◽  
R.L. Krauth-Siegel
Keyword(s):  
Trypanosoma Cruzi ◽  
Trypanothione Reductase
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