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Polyamine Metabolism: A Potential Therapeutic Target in Trypanosomes
Abstract
α-Difluoromethylornithine (RMI 71,782), a specific irreversible inhibitor of the first step in polyamine biosynthesis, that is, the formation of putrescine from ornithine by ornithine decarboxylase, cures mice infected with a virulent, rodent-passaged strain of Trypanosoma brucei bruce . This parasite is closely related to the trypanosomes that cause human sleeping sickness. The drug, which is remarkably nontoxic, was effective when administered in drinking water or by intubation. The ability of the compound to inhibit ornithine decarboxylase in vitro was demonstrated by the reduced amounts of putrescine synthesized from tritiated ornithine in Trypanosoma bruce suspensions. These observations direct attention to polyamine metabolism as a target for chemotherapy of parasitic diseases.
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Cited by
Drug repositioning: identifying and developing new uses for existing drugs
Ashburn, T. T., & Thor, K. B. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1468 · Cited by 3,237
Polyamine metabolism and function
Pegg, A. E., & McCann, P. P. (1982) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1982.243.5.c212 · Cited by 1,650
Self-citationBrun, R., Blum, J., Chappuis, F., & Burri, C. (2010) · The Lancet · doi:10.1016/s0140-6736(09)60829-1 · Cited by 926
Priotto, G., Kasparian, S., Mutombo, W., Ngouama, D., Ghorashian, S., Arnold, U., Ghabri, S., Baudin, E., Buard, V., Kazadi-Kyanza, S., et al. (2009) · The Lancet · doi:10.1016/s0140-6736(09)61117-x · Cited by 533
Drug repositioning for orphan diseases
Sardana, D., Zhu, C., Zhang, M., Gudivada, R. C., Yang, L., & Jegga, A. G. (2011) · Briefings in Bioinformatics · doi:10.1093/bib/bbr021 · Cited by 228
Metadata
- Authors
- Bacchi, C. J., Nathan, H. C., Hutner, S. H., McCann, P. P., & Sjoerdsma, A.
- Venue
- Science
- Published
- 1980-10-17
- Volume
- 210
- Issue
- 4467
- Pages
- 332-334
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1967701670
- Cited by
- 393
- References
- 0
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- closed
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- Bacchi, C. J., Nathan, H. C., Hutner, S. H., McCann, P. P., & Sjoerdsma, A. (1980). Polyamine Metabolism: A Potential Therapeutic Target in Trypanosomes. Science. https://doi.org/10.1126/science.6775372
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