Article

Efficacy of the bisbenzylisoquinoline alkaloids in acute and chronic Trypanosoma cruzi murine model.

Institut de Recherche pour le Développement, ex-ORSTOM, UR Sante, Paris, France.
International Journal of Antimicrobial Agents (impact factor: 4.13). 02/2000; 13(3):189-95. pp.189-95
Source: PubMed

ABSTRACT We have shown previously that daphnoline and cepharanthine are active against Trypanosoma cruzi and inhibited trypanothione reductase. The effects of oral treatments with daphnoline, cepharanthine and benznidazole were examined in Balb/c mice infected with T. cruzi acutely and chronically. In acute infections, parasitaemia was significantly reduced in the daphnoline-treated mice compared with controls and benznidazole-treated mice. The parasitological cure rate was increased in mice treated with daphnoline. Fifty days after infection, the negative serological response in both models was significantly different for the three tested drugs. Daphnoline showed the highest negative serological rate (48%). In chronically infected mice treated with daphnoline, we were unable to detect parasites in 70% of mice. The results obtained of oral treatment of daphnoline suggest that this bisbenzylisoquinoline may be useful in the treatment of acute and chronic Chagas' disease. This was not seen with cepharanthine, an excellent trypanothione reductase inhibitor.

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    Article: An insight on targets and patented drugs for chemotherapy of Chagas disease.
    Vilma G Duschak, Alicia S Couto
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    ABSTRACT: Chagas disease or American Trypanosomiasis, a parasitic infection typically spread by triatomine bugs, affects millions of people throughout Latin America. Current chemotherapy based on the nitroaromatic compounds, benznidazole and nifurtimox provides unsatisfactory results and suffers from considerable side effects and low efficacy. Therefore, there is an urgent need for new drugs to treat this neglected disease. Over the last two decades, new advances and understanding in the biology and the biochemistry of Trypanosoma cruzi has allowed the identification of multiple targets for Chagas disease chemotherapy. This review summarizes antichagasic agents obtained based on i) target metabolic biochemical pathways or parasite specific enzymes, ii) natural products and its derivatives, iii) design and synthesis of lead compounds. Related patents filed and issued from 2000 to early 2006 are also discussed. Most of them claimed inhibitors on specific parasite targets such as cysteine proteinase, sterol biosynthesis, protein farnesyltransferase, etc. Particularly, those related to cysteine proteinase inhibitors were the most represented. Natural products also displayed many anti-T cruzi lead compounds. In addition, a few patents claiming natural or synthetic compounds with antichagasic activity, disclosed no specific target. However, only a small proportion of all these patents displayed specific data of biological trypanocidal activity.
    Recent Patents on Anti-Infective Drug Discovery 02/2007; 2(1):19-51.
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Keywords

acute infections
 
Balb/c mice
 
benznidazole
 
benznidazole-treated mice
 
bisbenzylisoquinoline
 
chronic Chagas' disease
 
chronically
 
Daphnoline
 
daphnoline-treated mice
 
excellent trypanothione reductase inhibitor
 
highest negative serological rate
 
inhibited trypanothione reductase
 
mice
 
negative serological response
 
oral treatment
 
oral treatments
 
parasites
 
parasitological cure rate
 
T. cruzi acutely
 
Trypanosoma cruzi