ATP-Binding Cassette (ABC) transporters are efflux pumps frequently associated with multidrug resistance in many biological systems, including malaria. Antimalarial drug-resistance involves an ABC transporter, PfMDR1, a homologue of P-glycoprotein in humans. Twenty years of research have shown that several single nucleotide polymorphisms in pfmdr1 modulate in vivo and/or in vitro drug susceptib...

OBJECTIVES The in vitro and in vivo efficacy and drug-drug interactions of the novel semi-synthetic endoperoxide artemisone with standard antimalarials were investigated in order to provide the basis for the selection of the best partner drug. METHODS Antimalarial activity and drug interactions were evaluated in vitro against Plasmodium falciparum by the incorporation of [(3)H]hypoxanthine. I...

Using standard in vitro drug susceptibility methods, we assessed the antimalarial activity of 3 orally administered iron chelators (hydroxypyridinones) alone and in combination with conventional antimalarials drugs (quinine, mefloquine, artesunate, tetracycline, atovaquone) against a chloroquine-resistant Plasmodium falciparum isolate. When tested alone, all iron chelators and antimalarial comp...

The polyketide macrolactone FK506 inhibits the growth of Plasmodium falciparum in culture and the enzymatic (peptidyl-prolyl cis-trans isomerase [PPIase]) and chaperone activities of a recently identified P. falciparum FK506-binding protein (PfFKBP35). However, the potent immunosuppressive properties of FK506 exclude it from consideration as an antimalarial drug. We describe the antimalarial ac...

The control of malaria is challenged by drug resistance, and new antimalarial drugs are needed. New drug discovery efforts include consideration of hybrid compounds as potential multitarget antimalarials. Previous work from our group has demonstrated that hybrid structures resulting from cinnamic acid conjugation with heterocyclic moieties from well-known antimalarials present improved antimala...

Drug-resistant micro-organisms became widespread in the 20th Century, often with devastating consequences, in response to widespread use of natural and synthetic drugs against infectious diseases. Antimalarial resistance provides one of the earliest examples, following the introduction of new medicines that filled important needs for prophylaxis and treatment around the globe. In the present ch...

548 This symposium highlights selected topics in antimicro-bial resistance: community-acquired methicillin-resistant Staphylococcus aureus, malaria, reducing inappropriate antimicrobial drug prescribing for outpatient respiratory infections, and addressing the human health impact of antimicrobial drug use in food animals. Dr. Timothy Naimi discussed community-acquired methicillin-resistant Stap...

Cycloguanil pamoate is an antimalarial drug recently developed by Thompson et al. (1963) in the United States. It is closely allied to the existing drugs, proguanil and pyrimethamine, and when administered intramuscularly is slowly released and thus maintains an effective antiplasmodial blood level for a prolonged period. The advantages offered by a repository drug become obvious when considera...

Efforts have been intensified to search for more effective antimalarial agents because of the observed failure of some artemisinin-based combination therapy (ACT) treatments of malaria in Ghana. Xylopic acid, a pure compound isolated from the fruits of the Xylopia aethiopica, was investigated to establish its attributable prophylactic, curative antimalarial, and antipyretic properties. The anti...

BACKGROUND & OBJECTIVES Methylene blue (MB), a thiazine dye is used in the treatment of various methemoglobinaemias. However, sporadic reports have shown some antimalarial therapeutic effect when administered to patients with clinical manifestations of malaria. The inhibitory concentration of schizont maturation and antimalarial activity of MB have not been fully elucidated. The present study t...