Activities of DL-α-Difluoromethylarginine and Polyamine Analogues against Cryptosporidium parvum Infection in a T-Cell Receptor Alpha-Deficient Mouse Model

Activities of DL-α-Difluoromethylarginine and Polyamine Analogues against Cryptosporidium parvum Infection in a T-Cell Receptor Alpha-Deficient Mouse Model

The in vivo effectiveness of a series of conformationally restricted polyamine analogues alone and selected members in combination with DL-α-difluoromethylarginine against Cryptosporidium parvum infection in a T-cell receptor alpha-deficient mouse model was tested. Polyamine analogues were selected...

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Bibliographic Details
Published in:Antimicrobial Agents and Chemotherapy Vol. 51; no. 4; pp. 1234 - 1239
Main Authors: Yarlett, N, Harp, J.A, Wannemuehler, M.J, Morada, M, Bellcastro, J, Upton, S.J, Marton, L.J, Frydman, B.J
Format: Journal Article
Language:English
Published: United States American Society for Microbiology 01-04-2007
Subjects:
animal models
Animals
Antiprotozoal Agents
Antiprotozoal Agents - pharmacology
Antiprotozoal Agents - therapeutic use
Arginine
Arginine - analogs & derivatives
Arginine - pharmacology
Arginine - therapeutic use
Cryptosporidiosis - drug therapy
Cryptosporidium parvum
Cryptosporidium parvum - drug effects
difluoromethylarginine
disease control
Experimental Therapeutics
Genes, T-Cell Receptor alpha
Genes, T-Cell Receptor alpha - genetics
immunity
Mice
Mice, Knockout
Models, Animal
Polyamines
Polyamines - metabolism
Polyamines - pharmacology
Polyamines - therapeutic use
protozoal infections
receptors
T-cell receptor
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Summary:The in vivo effectiveness of a series of conformationally restricted polyamine analogues alone and selected members in combination with DL-α-difluoromethylarginine against Cryptosporidium parvum infection in a T-cell receptor alpha-deficient mouse model was tested. Polyamine analogues were selected from the extended bis(ethyl)-sym-homospermidine or bis(ethyl)-spermine backbone having cis or trans double bonds at the center of the molecule. The cis isomers were found to have significantly greater efficacy in both preventing and curing infection in a mouse model than the trans polyamine analogues when tested in a T-cell receptor alpha-deficient mouse model. When tested in combination with DL-α-difluoromethylarginine, the cis-restricted analogues were found to be more effective in preventing oocyst shedding. This study demonstrates the potential of polyamine analogues as anticryptosporidial agents and highlights the presence of multiple points in polyamine synthesis by this parasite that are susceptible to inhibition resulting in growth inhibition.
Bibliography:http://hdl.handle.net/10113/13634
http://dx.doi.org/10.1128/AAC.01040-06
ObjectType-Article-1
SourceType-Scholarly Journals-1
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Corresponding author. Mailing address: Haskins Laboratories, Pace University, 41 Park Row, New York, NY 10038. Phone: (212) 346-1853. Fax: (212) 346-1586. E-mail: nyarlett@pace.edu
ISSN:1098-6596
0066-4804
1098-6596
DOI:10.1128/AAC.01040-06