MEFAS, a hybrid of artesunate-mefloquine active against asexual stages of Plasmodium vivax in field isolates, inhibits malaria transmission
Autor: | Carlos Tong Rios, Julia Penna-Coutinho, Jansen Fernandes Medeiros, Nubia Boechat, Antoniana U. Krettli, Dhelio Batista Pereira, Maisa da Silva Araujo, Anna Caroline Campos Aguiar, Paula Miranda Sá |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Regular article
Plasmodium vivax Plasmodium falciparum Artesunate Antimalarial Drug resistance Infectious and parasitic diseases RC109-216 Drug resistant Antimalarials chemistry.chemical_compound parasitic diseases Malaria Vivax medicine Gametocyte Animals Humans Pharmacology (medical) Malaria Falciparum Artemisinin Pharmacology biology Mefloquine medicine.disease biology.organism_classification Virology Malaria New drugs Infectious Diseases chemistry Parasitology Transmission blocking medicine.drug |
Zdroj: | International Journal for Parasitology: Drugs and Drug Resistance, Vol 17, Iss, Pp 150-155 (2021) International Journal for Parasitology: Drugs and Drug Resistance |
ISSN: | 2211-3207 |
Popis: | Human malaria continues to be a public health problem and an important cause of morbidity and mortality in the world. Malaria control is achieved through both individual protection against mosquito bites and drug treatment, which is hampered by the spread of Plasmodium falciparum resistance to most antimalarials, including artemisinin derivatives. One of the key pharmacological strategies for controlling malaria is to block transmission of the parasites to their mosquito vectors. Following this rational, MEFAS, a synthetic hybrid salt derived from artesunate (AS) and mefloquine has been previously reported for its activity against asexual P. falciparum parasites in vitro, in addition to a pronounced reduction in the viability of mature gametocytes. Herein, MEFAS was tested against asexual forms of Plasmodium vivax and for its ability to block malaria transmission in Anopheles darlingi mosquitoes in a membrane feeding assay using P. vivax field isolates. MEFAS demonstrated high potency, with a IC50 of 6.5 nM against asexual forms of P. vivax. At 50 μM, MEFAS completely blocked oocyst formation in mosquitoes, regardless of the oocyst number in the control group. At lower doses, MEFAS reduced oocyst prevalence by greater than 20%. At equivalent doses, AS irregularly reduced oocyst formation and caused only slight inhibition of mosquito infections. These results highlight the potential of MEFAS as a novel transmission-blocking molecule, as well as its high blood schizonticidal activity against P. vivax and P. falciparum field isolates, representing a starting point for further development of a new drug with dual antimalarial activity. Graphical abstract Image 1 |
Databáze: | OpenAIRE |
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