application): Cryptosporidium parvum (C. parvum) is an apicomplexan parasite that is an emerging pathogen in the United States. The parasite invades gastrointestinal epithelial cells resulting in either asymptomatic infection or acute or chronic cholera-like diarrhea. Although, with adequate hydration, the symptoms are self-limiting in the immunocompetent population, the disease is particularly problematic in the immunocompromised patients where it can oftentimes be life threatening. In AIDS patients, it is one of the most common causes of debilitating diarrhea. Currently, there are no drugs available that can adequately cure the disease. Clearly, the development of therapeutic agents to eradicate C. parvum would be a scientifically and commercially successful venture. Recent evidence, according to the investigators, indicates that polyamine analogs have been successfully used as growth inhibitors of several pathogenic protozoa. Thus, there appears to be potential to design polyamine antagonists as selective anti-Cryptosporidial agents. Indeed, the investigators have designed some lead conformationally constrained polyamines that have growth inhibitory effects in C. parvum.
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| Yarlett, Nigel; Waters, W Ray; Harp, James A et al. (2007) Activities of DL-alpha-difluoromethylarginine and polyamine analogues against Cryptosporidium parvum infection in a T-cell receptor alpha-deficient mouse model. Antimicrob Agents Chemother 51:1234-9 |
| Yarlett, Nigel; Wu, Gang; Waters, W Ray et al. (2007) Cryptosporidium parvum spermidine/spermine N1-acetyltransferase exhibits different characteristics from the host enzyme. Mol Biochem Parasitol 152:170-80 |
| Waters, W R; Frydman, B; Marton, L J et al. (2000) [(1)N,(12)N]Bis(Ethyl)-cis-6,7-dehydrospermine: a new drug for treatment and prevention of Cryptosporidium parvum infection of mice deficient in T-cell receptor alpha. Antimicrob Agents Chemother 44:2891-4 |
