Biomaterial Database

In vitro activity of mitochondrial ATP synthetase inhibitors against Plasmodium falciparum. 1994

L K Basco, and J Le Bras

Centre National de Référence pour la Chimiosensibilité du Paludisme, Hôpital Bichat-Claude Bernard, Paris, France.

The mitochondrion appears to be essential for the growth of asexual, intraerythrocytic stages of Plasmodium falciparum and may thus be a suitable chemotherapeutic target. The in vitro activity of almitrine, a mitochondrial ATP synthetase inhibitor used for the treatment of hypoxemia, was compared with other mitochondrial inhibitors against chloroquine-susceptible and chloroquine-resistant P. falciparum using an isotopic semimicro drug susceptibility assay. The 50% inhibitory concentration (IC50) values of almitrine (range: 2.6-19.8 microM) were within similar range of values of other mitochondrial ATP synthetase inhibitors and doxycycline, a mitochondrial protein synthesis inhibitor. Almitrine was equally active against chloroquine-susceptible and chloroquine-resistant parasites. Drug combination studies showed no interaction between chloroquine and almitrine. Our results suggest that almitrine, a clinically safe drug, may represent a lead compound with a specific target against the mitochondrial ATP synthetase which may be useful for antimalarial chemotherapy.

UI	MeSH Term	Description	Entries
D008928	Mitochondria	Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)	Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
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
D011794	Quercetin	A flavonol widely distributed in plants. It is an antioxidant, like many other phenolic heterocyclic compounds. Glycosylated forms include RUTIN and quercetrin.	3,3',4',5,7-Pentahydroxyflavone,Dikvertin
D002738	Chloroquine	The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.	Aralen,Arechine,Arequin,Chingamin,Chlorochin,Chloroquine Sulfate,Chloroquine Sulphate,Khingamin,Nivaquine,Sulfate, Chloroquine,Sulphate, Chloroquine
D003891	Desipramine	A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.	Desmethylimipramine,Apo-Desipramine,Demethylimipramine,Desipramine Hydrochloride,Norpramin,Novo-Desipramine,Nu-Desipramine,PMS-Desipramine,Pertofran,Pertofrane,Pertrofran,Petylyl,Ratio-Desipramine,Apo Desipramine,Hydrochloride, Desipramine,Novo Desipramine,Nu Desipramine,PMS Desipramine,Ratio Desipramine
D004024	Dicyclohexylcarbodiimide	A carbodiimide that is used as a chemical intermediate and coupling agent in peptide synthesis. (From Hawley's Condensed Chemical Dictionary, 12th ed)	DCCD
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
D004912	Erythrocytes	Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.	Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006180	Proton-Translocating ATPases	Multisubunit enzymes that reversibly synthesize ADENOSINE TRIPHOSPHATE. They are coupled to the transport of protons across a membrane.	ATP Dependent Proton Translocase,ATPase, F0,ATPase, F1,Adenosinetriphosphatase F1,F(1)F(0)-ATPase,F1 ATPase,H(+)-Transporting ATP Synthase,H(+)-Transporting ATPase,H(+)ATPase Complex,Proton-Translocating ATPase,Proton-Translocating ATPase Complex,Proton-Translocating ATPase Complexes,ATPase, F(1)F(0),ATPase, F0F1,ATPase, H(+),Adenosine Triphosphatase Complex,F(0)F(1)-ATP Synthase,F-0-ATPase,F-1-ATPase,F0F1 ATPase,F1-ATPase,F1F0 ATPase Complex,H(+)-ATPase,H(+)-Transporting ATP Synthase, Acyl-Phosphate-Linked,H+ ATPase,H+ Transporting ATP Synthase,H+-Translocating ATPase,Proton-Translocating ATPase, F0 Sector,Proton-Translocating ATPase, F1 Sector,ATPase Complex, Proton-Translocating,ATPase Complexes, Proton-Translocating,ATPase, H+,ATPase, H+-Translocating,ATPase, Proton-Translocating,Complex, Adenosine Triphosphatase,Complexes, Proton-Translocating ATPase,F 0 ATPase,F 1 ATPase,F0 ATPase,H+ Translocating ATPase,Proton Translocating ATPase,Proton Translocating ATPase Complex,Proton Translocating ATPase Complexes,Proton Translocating ATPase, F0 Sector,Proton Translocating ATPase, F1 Sector,Triphosphatase Complex, Adenosine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man