Biomaterial Database

Synergistic antimalarial activity of pyrimethamine and sulfadoxine against Plasmodium falciparum in vitro. 1984

J D Chulay, and W M Watkins, and D G Sixsmith

Two strains of Plasmodium falciparum were tested in vitro for sensitivity to the dihydrofolate reductase inhibitor pyrimethamine, the p-aminobenzoic acid (PABA) analogue sulfadoxine, and combinations of both drugs. One strain was sensitive and one resistant to pyrimethamine in vitro. Parasites cultured in medium containing neither folic acid nor PABA were inhibited by 10(-6) M sulfadoxine, a concentration well below that achievable after therapeutic dosage. Folic acid added to this medium at a physiological concentration of 0.01 mg/liter caused a 1,000-fold reduction in sulfadoxine activity; a 100-fold higher concentration of folic acid caused a 10-fold reduction in pyrimethamine activity. Sulfadoxine in a concentration of 10(-7) M was able to potentiate pyrimethamine activity in PABA-free medium with no added folic acid or with 0.01 mg folic acid/liter. These data indicate that P. falciparum can utilize exogenous folic acid, and suggest that sulfadoxine may potentiate pyrimethamine activity by simultaneous inhibition of dihydrofolate reductase.

UI	MeSH Term	Description	Entries
D010129	4-Aminobenzoic Acid	An aminobenzoic acid isomer that combines with pteridine and GLUTAMIC ACID to form FOLIC ACID. The fact that 4-aminobenzoic acid absorbs light throughout the UVB range has also resulted in its use as an ingredient in SUNSCREENS.	PABA,p-Aminobenzoic Acid,para-Aminobenzoic Acid,4-Aminobenzoic Acid, Potassium Salt,Aminobenzoic Acid (USP),Epit Vit,Epitelplast,Hachemina,Magnesium para-Aminobenzoate,Pabasan,Paraminan,Paraminol,Potaba,Potassium 4-Aminobenzoate,Potassium Aminobenzoate,4 Aminobenzoic Acid,4 Aminobenzoic Acid, Potassium Salt,4-Aminobenzoate, Potassium,Aminobenzoate, Potassium,Potassium 4 Aminobenzoate,p Aminobenzoic Acid,para Aminobenzoic Acid,para-Aminobenzoate, Magnesium
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
D011739	Pyrimethamine	One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.	Chloridin,Daraprim,Malocide,Tindurine
D003470	Culture Media	Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.	Media, Culture
D004353	Drug Evaluation, Preclinical	Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.	Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005492	Folic Acid	A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.	Pteroylglutamic Acid,Vitamin M,Folacin,Folate,Folic Acid, (D)-Isomer,Folic Acid, (DL)-Isomer,Folic Acid, Calcium Salt (1:1),Folic Acid, Monopotassium Salt,Folic Acid, Monosodium Salt,Folic Acid, Potassium Salt,Folic Acid, Sodium Salt,Folvite,Vitamin B9,B9, Vitamin
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
D013413	Sulfadoxine	A long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections.	Sulformethoxine,Sulforthomidine,Fanasil,Ro 4-4393,Sulformetoxine,Sulphormetoxin,Sulphorthodimethoxine,Ro 4 4393,Ro 44393
D013424	Sulfanilamides	Compounds based on 4-aminobenzenesulfonamide. The '-anil-' part of the name refers to aniline.	Sulphanilamides