Artesunate Activation by Heme in an Aqueous Medium
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:496 |
|---|---|
| Enthalten in: |
Inorganica chimica acta - 496(2019) vom: 01. Okt. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Heller, Laura [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 01.10.2020 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1016/j.ica.2019.119029 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM314049940 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM314049940 | ||
| 003 | DE-627 | ||
| 005 | 20231225151907.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ica.2019.119029 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1046.xml |
| 035 | |a (DE-627)NLM314049940 | ||
| 035 | |a (NLM)32831389 | ||
| 035 | |a (PII)119029 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Heller, Laura |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Artesunate Activation by Heme in an Aqueous Medium |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 01.10.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Roepe, Paul D |e verfasserin |4 aut | |
| 700 | 1 | |a de Dios, Angel C |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Inorganica chimica acta |d 1998 |g 496(2019) vom: 01. Okt. |w (DE-627)NLM098110314 |x 0020-1693 |7 nnns |
| 773 | 1 | 8 | |g volume:496 |g year:2019 |g day:01 |g month:10 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ica.2019.119029 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 496 |j 2019 |b 01 |c 10 | ||