Biomaterial Database

In vitro activity of atovaquone against the African isolates and clones of Plasmodium falciparum. 1995

L K Basco, and O Ramiliarisoa, and J Le Bras

Centre National de Reference de la Chimiosensibilite du Paludisme, Laboratoire de Parasitologie, Hopital Bichat-Claude Bernard, Paris, France.

The in vitro activity of atovaquone (566C80) was evaluated and compared with that of chloroquine, quinine, mefloquine, halofantrine, artemether, pyrimethamine, and cycloguanil against African isolates and clones of Plasmodium falciparum using an isotopic, semimicro, drug susceptibility test. Atovaquone was highly active against the chloroquine-susceptible L-3 (geometric mean 50% inhibitory concentration [IC50] = 0.978 nM) and L-16 clones (mean IC50 = 0.680 nM) and against the multidrug-resistant FCM 29 clone (mean IC50 = 1.76 nM). Similar low IC50 values for atovaquone were observed against the chloroquine-susceptible isolates (n = 35; geometric mean IC50 = 0.889 nM) and the chloroquine-resistant parasites (n = 26; geometric mean IC50 = 0.906 nM). The in vitro responses between atovaquone and the other antimalarial drugs were not correlated, indicating the absence of in vitro cross-resistance. The high in vitro activity of atovaquone without any in vitro evidence for cross-resistance with other antimalarial drugs against the naturally occurring malaria parasites is a factor that favors further development of the drug for clinical use.

UI	MeSH Term	Description	Entries
D009285	Naphthoquinones	Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.	Naphthalenediones,Naphthazarins,Naphthoquinone
D010963	Plasmodium falciparum	A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.	Plasmodium falciparums,falciparums, Plasmodium
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000962	Antimalarials	Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)	Anti-Malarial,Antimalarial,Antimalarial Agent,Antimalarial Drug,Anti-Malarials,Antimalarial Agents,Antimalarial Drugs,Agent, Antimalarial,Agents, Antimalarial,Anti Malarial,Anti Malarials,Drug, Antimalarial,Drugs, Antimalarial
D053626	Atovaquone	A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols.	2-(4-(4'-chlorophenyl)cyclohexyl)-3-hydroxy-1,4-naphthoquinone,2-(trans-4-(4-chlorophenyl)cyclohexyl)-3-hydroxy-1,4-naphthoquinone,566C,566C80,566C80 hydroxynaphthoquinone,Mepron,Wellvone,compound 566,hydroxynaphthoquinone 566C80,hydroxynaphthoquinone, 566C80