scholarly journals The Anti-Influenza Virus Drug Rimantadine Has Trypanocidal Activity

1999 ◽  
Vol 43 (4) ◽  
pp. 985-987 ◽  
Author(s):  
John M. Kelly ◽  
Michael A. Miles ◽  
Anita C. Skinner
Keyword(s):  
Influenza Virus ◽  
Trypanosoma Cruzi ◽  
Trypanosoma Brucei ◽  
Leishmania Major ◽  
Inhibitory Concentration ◽  
Trypanocidal Activity ◽  
African Trypanosome ◽  
Internal Ph ◽  
Trypanosomatid Parasites ◽  
Ph Dependent

ABSTRACT We report here that bloodstream forms of the African trypanosome,Trypanosoma brucei, are sensitive to the anti-influenza virus drug rimantadine (50% inhibitory concentration of 1.26 μg ml−1 at pH 7.4). The activity is pH dependent and is consistent with a mechanism involving inhibition of the ability to regulate internal pH. Rimantadine is also toxic to the trypanosomatid parasites Trypanosoma cruzi and Leishmania major.

scholarly journals Sugar Nucleotide Pools of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major

2007 ◽  
Vol 6 (8) ◽  
pp. 1450-1463 ◽  
Author(s):  
Daniel C. Turnock ◽  
Michael A. J. Ferguson
Keyword(s):  
Trypanosoma Brucei ◽  
Leishmania Major ◽  
Multiple Reaction Monitoring ◽  
Sugar Nucleotides ◽  
Sugar Nucleotide ◽  
Nucleotide Pools ◽  
Trypanosomatid Parasites ◽  
Promastigote Form ◽  
And Function ◽  
Considerable Body

ABSTRACT The cell surface glycoconjugates of trypanosomatid parasites are intimately involved in parasite survival, infectivity, and virulence in their insect vectors and mammalian hosts. Although there is a considerable body of work describing their structure, biosynthesis, and function, little is known about the sugar nucleotide pools that fuel their biosynthesis. In order to identify and quantify parasite sugar nucleotides, we developed an analytical method based on liquid chromatography-electrospray ionization-tandem mass spectrometry using multiple reaction monitoring. This method was applied to the bloodstream and procyclic forms of Trypanosoma brucei, the epimastigote form of T. cruzi, and the promastigote form of Leishmania major. Five sugar nucleotides, GDP-α-d-mannose, UDP-α-d-N-acetylglucosamine, UDP-α-d-glucose, UDP-α-galactopyranose, and GDP-β-l-fucose, were common to all three species; one, UDP-α-d-galactofuranose, was common to T. cruzi and L. major; three, UDP-β-l-rhamnopyranose, UDP-α-d-xylose, and UDP-α-d-glucuronic acid, were found only in T. cruzi; and one, GDP-α-d-arabinopyranose, was found only in L. major. The estimated demands for each monosaccharide suggest that sugar nucleotide pools are turned over at very different rates, from seconds to hours. The sugar nucleotide survey, together with a review of the literature, was used to define the routes to these important metabolites and to annotate relevant genes in the trypanosomatid genomes.

scholarly journals Identification of New Kinetoplast DNA Replication Proteins in Trypanosomatids Based on Predicted S-Phase Expression and Mitochondrial Targeting

2007 ◽  
Vol 6 (12) ◽  
pp. 2303-2310 ◽  
Author(s):  
Yue Li ◽  
Yu Sun ◽  
Jane C. Hines ◽  
Dan S. Ray
Keyword(s):  
Gene Expression ◽  
Trypanosoma Brucei ◽  
Leishmania Major ◽  
S Phase ◽  
Regulatory Sequences ◽  
Replication Proteins ◽  
Kinetoplast Dna ◽  
Mitochondrial Targeting ◽  
Novel Proteins ◽  
Trypanosomatid Parasites

ABSTRACT Trypanosomatid parasites contain an unusual form of mitochondrial DNA (kinetoplast DNA [kDNA]) consisting of a catenated network of several thousand minicircles and a smaller number of maxicircles. Many of the proteins involved in the replication and division of kDNA are likely to have no counterparts in other organisms and would not be identified by similarity to known replication proteins in other organisms. A new kDNA replication protein conserved in kinetoplastids has been identified based on the presence of posttranscriptional regulatory sequences associated with S-phase gene expression and predicted mitochondrial targeting. The Leishmania major protein P105 (LmP105) and Trypanosoma brucei protein P93 (TbP93) localize to antipodal sites flanking the kDNA disk, where several other replication proteins and nascent minicircles have been localized. Like some of these kDNA replication proteins, the LmP105 protein is only present at the antipodal sites during S phase. RNA interference (RNAi) of TbP93 expression resulted in a cessation of cell growth and the loss of kDNA. Nicked/gapped forms of minicircles, the products of minicircle replication, were preferentially lost from the population of free minicircles during RNAi, suggesting involvement of TbP93 in minicircle replication. This approach should allow the identification of other novel proteins involved in the duplication of kDNA.

Trypanocidal activity of fruits extracts of Solanum lycocarpum St. Hill. on Trypanosoma cruzi and Trypanosoma brucei strains

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
GZ Martins ◽  
NO Magalhães ◽  
FAJ Silva ◽  
AMA Velásquez ◽  
DF Rodrigues ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Trypanosoma Brucei ◽  
Trypanocidal Activity

The use of Sulfonamide Derivatives in the Treatment of Trypanosomatid Parasites including Trypanosoma cruzi, Trypanosoma brucei, and Leishmania ssp

2020 ◽  
Vol 16 (1) ◽  
pp. 24-38 ◽  
Author(s):  
Cauê B. Scarim ◽  
Rafael C. Chelucci ◽  
Jean L. dos Santos ◽  
Chung M. Chin
Keyword(s):  
Trypanosoma Cruzi ◽  
Trypanosoma Brucei ◽  
Human African Trypanosomiasis ◽  
Neglected Tropical Diseases ◽  
Economic Incentive ◽  
Tropical Diseases ◽  
Lipinski’S Rule ◽  
Novel Drugs ◽  
Trypanosomatid Parasites ◽  
Research And Policy

More than 10 million people around the world are afflicted by Neglected Tropical Diseases, such as Chagas Disease, Human African Trypanosomiasis, and Leishmania. These diseases mostly occur in undeveloped countries that suffer from a lack of economic incentive, research, and policy for new compound development. Sulfonamide moieties are effective scaffolds present in several compounds that are determinants to treat various diseases, principally neglected tropical diseases. This review article examines the contribution of these scaffolds in medicinal chemistry in the last five years, focusing on three trypanosomatid parasites: Trypanosoma cruzi, Trypanosoma brucei, and Leishmania ssp. We also present perspectives for their use in drug designs in an effort to contribute to new drug development. In addition, we consider the physicochemical parameters, whose molecules all presented according to Lipinski's rule. The correlation between the selective index and LogP was evaluated, showing that sulfonamide derivatives can act differently against each trypanosomatid parasite. Moreover, the approaches of novel drugs and technologies are very important for the eventual drug discovery against trypanosomatid diseases.

scholarly journals In vitro trypanocidal activities of new S-adenosylmethionine decarboxylase inhibitors.

1996 ◽  
Vol 40 (6) ◽  
pp. 1442-1447 ◽  
Author(s):  
R Brun ◽  
Y Bühler ◽  
U Sandmeier ◽  
R Kaminsky ◽  
C J Bacchi ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Leishmania Donovani ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Trypanocidal Activity ◽  
Adenosylmethionine Decarboxylase ◽  
Low Concentrations ◽  
Decarboxylase Inhibitors ◽  
Dose Dependent

A series of novel aromatic derivatives based on the structure of methylglyoxal bis(guanylhydrazone) (MGBG) was examined for in vitro antitrypanosomal activities and cytotoxicities for human cells. One-third of the compounds tested showed trypanocidal activity at concentrations below 0.5 microM after an incubation period of 72 h. Structure-activity analysis revealed that bicyclic compounds with homocyclic rings and unmodified termini were the most active compounds. Results obtained in three laboratories employing different methods and trypanosome populations consistently ranked compound CGP 40215A highest. This compound had a 50% inhibitory concentration of 0.0045 microM for Trypanosoma brucei rhodesiense, was also active against other trypanosome species, including a multidrug-resistant Trypanosoma brucei brucei, and was significantly less toxic than other compounds tested for a human adenocarcinoma cell line, with a 50% inhibitory concentration of 1.14 mM. The effect of CGP 40215A was time and dose dependent, and low concentrations of the compound required exposure times of > 2 days to exert trypanocidal activity. Compounds were inactive against Leishmania donovani and Trypanosoma cruzi amastigotes in murine macrophages in vitro.

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