Synthesis and in Vitro Antiprotozoal Activity of Bisbenzofuran Cations
| Autor: | Tanja Wenzler, James Edwin Hall, Svetlana M. Bakunova, Stanislav A. Bakunov, Reto Brun, Karl A. Werbovetz, Richard R. Tidwell, Todd Barszcz |
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| Rok vydání: | 2007 |
| Předmět: |
Trypanosoma brucei rhodesiense
medicine.drug_class Stereochemistry Plasmodium falciparum Leishmania donovani Trypanosoma brucei Chemical synthesis Antimalarials Structure-Activity Relationship Cations parasitic diseases Drug Discovery medicine Animals Benzofurans biology Chemistry Biological activity biology.organism_classification Trypanocidal Agents Rats Antiprotozoal Molecular Medicine Pentamidine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 50:5807-5823 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm0708634 |
| Popis: | Forty three cationic bisbenzofurans were synthesized either by interaction of o-hydroxyaldehydes with alpha-halogenated ketones followed by intramolecular ring closure or by a copper- or palladium-mediated heteroannulation of substituted o-iodophenols with terminal acetylenes. In vitro antiprotozoal activities of compounds 1-43 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and cytotoxicity against mammalian cells were influenced by the position and the type of cationic substituents as well as the length of the carbon linker between aromatic moieties. One bisamidine displayed an antitrypanosomal efficacy comparable to that of pentamidine and melarsoprol. Twenty two compounds were more potent than pentamidine and seven dications were more effective than artemisinin against P. falciparum. Eight bisbenzofurans displayed activity against L. donovani superior to that of pentamidine. Overall, bisamidines connected by two-carbon linkers exhibited the highest efficacies against T. b. rhodesiense, P. falciparum, and L. donovani. |
| Databáze: | OpenAIRE |
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