4-Aminoquinolines block heme iron reactivity and interfere with artemisinin action - PubMed
4 hours ago
- #heme
- #antimalarial
- #quinoline
- 4-Aminoquinolines block heme iron reactivity and interfere with artemisinin action.
- Artemisinin-based combination therapies (ACTs) are the main treatment for Plasmodium falciparum malaria, despite reports of treatment failure.
- Chloroquine (CQ), piperaquine (PPQ), and amodiaquine antagonize dihydroartemisinin (DHA), the active metabolite of artemisinins.
- CQ-DHA antagonism is exacerbated in CQ-resistant parasites, leading to a superantagonistic phenotype.
- CQ co-treatment confers artemisinin resistance to Kelch 13 wild-type parasites.
- Quinolines block artemisinin activation by rendering cytosolic heme inert.
- Interactions of proposed triple ACT (DHA-PPQ-mefloquine) and OZ439-quinoline combinations are antagonistic.
- Peroxide-quinolines may have liabilities as combination therapies.