O-Alkoxyamidine Prodrugs of Furamidine: In Vitro Transport and Microsomal Metabolism as Indicators of in Vivo Efficacy in a Mouse Model of Trypanosoma brucei rhodesiense Infection
| Autor: | James Edwin Hall, Mariappan Anbazhagan, John H. Ansede, David W. Boykin, Reto Brun, Judy D. Easterbrook |
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| Rok vydání: | 2004 |
| Předmět: |
Trypanosoma brucei rhodesiense
Administration Oral In Vitro Techniques Trypanosoma brucei Permeability Mice Structure-Activity Relationship In vivo Drug Discovery Animals Humans Prodrugs Trypanocidal agent biology Chemistry Biological Transport Biological activity Prodrug biology.organism_classification Trypanocidal Agents In vitro Benzamidines Disease Models Animal Trypanosomiasis African Biochemistry Microsomes Liver Microsome Molecular Medicine Caco-2 Cells |
| Zdroj: | Journal of Medicinal Chemistry. 47:4335-4338 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm030604o |
| Popis: | Five O-alkoxyamidine analogues of the prodrug 2,5-bis[4-methoxyamidinophenyl]furan were synthesized and evaluated against Trypanosoma brucei rhodesiense in the STIB900 mouse model by oral administration. The observed in vivo activity of these prodrugs demonstrates that compounds with an O-methoxyamidine or O-ethoxyamidine group effectively cured all trypanosome-infected mice, whereas prodrugs with larger side-chains did not completely cure the mice. Permeability across Caco-2 cell monolayers and microsomal metabolism were used to identify the underlying mechanisms of prodrug efficacy. |
| Databáze: | OpenAIRE |
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