Activation of artemisinin and heme degradation in Leishmania tarentolae promastigotes: A possible link.
Animals
Artemisinins
/ chemistry
Cell Line
Cell Survival
/ drug effects
Electron Spin Resonance Spectroscopy
Free Radicals
/ chemistry
Heme
/ chemistry
Heme Oxygenase (Decyclizing)
/ metabolism
Iron
/ metabolism
Leishmania
/ cytology
Macrophages
/ drug effects
Mice
Oxidation-Reduction
/ drug effects
Peroxides
/ chemistry
Spores, Protozoan
/ cytology
Artemisinin
Endoperoxide
Heme
Leishmania
Radicals
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
27
09
2019
accepted:
26
11
2019
pubmed:
2
12
2019
medline:
18
8
2020
entrez:
2
12
2019
Statut:
ppublish
Résumé
Endoperoxides (EPs) appear to be promising drug candidates against protozoal diseases, including malaria and leishmaniasis. Previous studies have shown that these drugs need an intracellular activation to exert their pharmacological potential. The efficiency of these drugs is linked to the extensive iron demand of these intracellular protozoal parasites. An essential step of the activation mechanism of these drugs is the formation of radicals in Leishmania. Iron is a known trigger for intracellular radical formation. However, the activation of EPs by low molecular iron or by heme iron may strongly depend on the structure of the EPs themselves. In this study, we focused on the activation of artemisinin (Art) in Leishmania tarentolae promastigotes (LtP) in comparison to reference compounds. Viability assays in different media in the presence of different iron sources (hemin/fetal calf serum) showed that IC
Identifiants
pubmed: 31786259
pii: S0006-2952(19)30436-8
doi: 10.1016/j.bcp.2019.113737
pmc: PMC7116464
mid: EMS107384
pii:
doi:
Substances chimiques
Artemisinins
0
Free Radicals
0
Peroxides
0
Heme
42VZT0U6YR
Iron
E1UOL152H7
Heme Oxygenase (Decyclizing)
EC 1.14.14.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113737Subventions
Organisme : Austrian Science Fund FWF
ID : P 27814
Pays : Austria
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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