Trypanosoma cruzi: Inhibition of Parasite Growth and Respiration by Oxazolo(thiazolo)pyridine Derivatives and Its Relationship to Redox Potential and Lipophilicity

2001 ◽  
Vol 99 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Juan Diego Maya ◽  
Antonio Morello ◽  
Yolanda Repetto ◽  
Andrés Rodrı́guez ◽  
Pilar Puebla ◽  
...  
2013 ◽  
Vol 56 (6) ◽  
pp. 2556-2567 ◽  
Author(s):  
Grasiella Andriani ◽  
Emanuele Amata ◽  
Joel Beatty ◽  
Zeke Clements ◽  
Brian J. Coffey ◽  
...  

2016 ◽  
Vol 249 (4) ◽  
pp. 475-481 ◽  
Author(s):  
Chantal Reigada ◽  
Melisa Sayé ◽  
Edward Valera Vera ◽  
Darío Balcazar ◽  
Laura Fraccaroli ◽  
...  

2011 ◽  
Vol 204 (6) ◽  
pp. 951-961 ◽  
Author(s):  
Heloisa D’Avila ◽  
Célio G. Freire-de-Lima ◽  
Natalia R. Roque ◽  
Livia Teixeira ◽  
Christina Barja-Fidalgo ◽  
...  

2007 ◽  
Vol 15 (5) ◽  
pp. 2106-2119 ◽  
Author(s):  
João Neres ◽  
Pascal Bonnet ◽  
Philip N. Edwards ◽  
Pravin L. Kotian ◽  
Alejandro Buschiazzo ◽  
...  

Parasitology ◽  
1982 ◽  
Vol 84 (3) ◽  
pp. 511-526 ◽  
Author(s):  
G. T. Williams ◽  
L. Hudson

SummaryThe design and operation of a modular, bacteriological continuous-flow culture system have been adapted for the growth of Trypanosoma cruzi epimastigotes in simple monophasic media. The system was designed to achieve a minimum of 200 days of continuous culture and provision was made for the continuous supply of medium and collection of parasites under sterile conditions. The system provides large quantities of epimastigotes with homogeneous morphology and uniform viability. The system also lends itself tothe analysis of the factors which affect parasite growth. We have examined the effects of changes in environmental parameters on epimastigote growth rate. Optimal growth was observed at 27 °C. The rate ofstirring of the culture had a small but definable effect on the growth rate, which was greatest at 80 r.p.m. Growth was only slightly affected by the level of dissolved oxygen between 10 and 50% saturation, but was inhibited at higher concentrations. Growth was slower at extreme values of pH but showed a broad optimum around pH 7·4.


PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130099 ◽  
Author(s):  
Ignacio M. Durante ◽  
María de los Milagros Cámara ◽  
Carlos A. Buscaglia

2021 ◽  
Vol 22 (2) ◽  
pp. 688 ◽  
Author(s):  
Nieves Martinez-Peinado ◽  
Clara Martori ◽  
Nuria Cortes-Serra ◽  
Julian Sherman ◽  
Ana Rodriguez ◽  
...  

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects over 6 million people worldwide. Development of new drugs to treat this disease remains a priority since those currently available have variable efficacy and frequent adverse effects, especially during the long regimens required for treating the chronic stage of the disease. T. cruzi modulates the host cell-metabolism to accommodate the cell cytosol into a favorable growth environment and acquire nutrients for its multiplication. In this study we evaluated the specific anti-T. cruzi activity of nine bio-energetic modulator compounds. Notably, we identified that 17-DMAG, which targets the ATP-binding site of heat shock protein 90 (Hsp90), has a very high (sub-micromolar range) selective inhibition of the parasite growth. This inhibitory effect was also highly potent (IC50 = 0.27 μmol L−1) against the amastigote intracellular replicative stage of the parasite. Moreover, molecular docking results suggest that 17-DMAG may bind T. cruzi Hsp90 homologue Hsp83 with good affinity. Evaluation in a mouse model of chronic T. cruzi infection did not show parasite growth inhibition, highlighting the difficulties encountered when going from in vitro assays onto preclinical drug developmental stages.


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