Artesunate activation by heme in an aqueous medium
| Autor: | Paul D. Roepe, Laura E. Heller, Angel C. de Dios |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Drug
Combination therapy Heme binding 010405 organic chemistry media_common.quotation_subject Quinoline Glutathione 010402 general chemistry 01 natural sciences Medicinal chemistry Article 0104 chemical sciences Inorganic Chemistry chemistry.chemical_compound chemistry Artesunate Materials Chemistry medicine Physical and Theoretical Chemistry Artemisinin Heme medicine.drug media_common |
| Zdroj: | Inorganica Chim Acta |
| ISSN: | 0020-1693 |
| DOI: | 10.1016/j.ica.2019.119029 |
| Popis: | The reaction between the antimalarial drug artesunate (ATS) and ferriprotoporphyrin_(IX) (FPIX) in the presence of glutathione (GSH) has been monitored by nuclear magnetic resonance (NMR) spectroscopy. By following the disappearance of resonances of protons near the endoperoxide group in ATS, the rate at which the drug is activated can be directly measured. In an aqueous medium, the rate of ATS activation is limited by the rate of reduction of the FPIX Fe(III) center by GSH. The reaction is observed to slow dramatically in the presence of other heme binding antimalarial drugs. These findings explain the long observed antagonism between artemisinin derivatives and quinoline-based drugs. This discovery suggests that combination therapy that involves artemisinin or any of its derivatives and a quinoline-based drug may be compromised. |
| Databáze: | OpenAIRE |
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