Synthesis and antimalarial efficacy of two-carbon-linked, artemisinin-derived trioxane dimers in combination with known antimalarial drugs
| Autor: | Bryan T. Mott, Gary H. Posner, Cathy D. Moore, Abhai K. Tripathi, David J. Sullivan, Maxime A. Siegler |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Models Molecular Combination therapy Plasmodium berghei First line Molecular Conformation Chemistry Techniques Synthetic Pharmacology Article Single oral dose chemistry.chemical_compound Antimalarials Mice Drug Discovery parasitic diseases medicine Animals Drug Interactions Artemisinin Natural product biology Antimalarial chemotherapy Stereoisomerism biology.organism_classification medicine.disease Artemisinins Carbon chemistry Molecular Medicine Dimerization Malaria medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 56(6) |
| ISSN: | 1520-4804 |
| Popis: | Malaria continues to be a difficult disease to eradicate, largely due to the widespread populations it affects and to the resistance that malaria parasites have developed against once very potent therapies. The natural product artemisinin has been a boon for antimalarial chemotherapy as artemisinin combination therapy (ACT) has become the first line of chemotherapy. Because the threat of resistance is always on the horizon, it is imperative to continually identify new treatments, comprised of both advanced analogs of all antimalarial drugs, especially artemisinin, as well as the exploration of novel combinations, ideally with distinct mechanisms of action. Here we report, for the first time, synthesis of a series of two-carbon linked artemisinin-derived dimers, their unique structural features, and demonstration of their antimalarial efficacy via single oral dose administration in two 60-day survival studies of Plasmodium berghei-infected mice. Several of the new endoperoxide chemical entities consistently demonstrated excellent antimalarial efficacy, and combinations with two non-peroxide antimalarial drugs have been studied. |
| Databáze: | OpenAIRE |
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