Increasing reports of multidrug-resistant malaria parasites urge the discovery of new effective drugs with different chemical scaffolds. Protein kinases play a key role in many cellular processes such as signal transduction and cell division, making them interesting targets in many diseases. Protein kinase 7 (PK7) is an orphan kinase from the Plasmodium genus, essential for the sporogonic cycle of these parasites.
The current decline in antimalarial drug efficacy due to the evolution of resistant Plasmodium strains calls for new strategies capable of improving the bioavailability of antimalarials, especially of those whose lipophilic character imparts them a low solubility in biological fluids. Here we have designed, synthesized and characterized amphiphilic zwitterionic block copolymers forming nanoparticles capable of penetrating the intestinal epithelium that can be used for oral administration. Poly(butyl methacrylate-co-morpholinoethyl sulfobetaine methacrylate) (PBMA-MESBMA)-based nanoparticles exhibited a specific targeting of Plasmodium falciparum-infected vs. parasite-free red blood cells (74.8%/0.8% respectively), which was maintained upon encapsulation of the lipophilic antimalarial drug curcumin (82.6%/0.3%).
The asexual blood stages of the Plasmodium berghei life cycle including merozoites are attractive targets for transmission blocking vaccines and drugs. Improved understanding of P. berghei life cycle stage growth and development would provide new opportunities to evaluate antimalarial vaccines and drugs.
Quinoline antimalarials cause drug-induced electrocardiograph QT prolongation, a potential risk factor for torsade de pointes. The effects of currently used antimalarials on the electrocardiogram were assessed in pregnant women with malaria. Pregnant women with microscopy-confirmed parasitaemia of any malaria species were enrolled in an open-label randomised controlled trial on the Thailand-Myanmar border in 2010-2016. Patients were randomised to the standard regimen dihydroartemisinin-piperaquine (DP), artesunate-mefloquine (ASMQ), or an extended regimen of artemether-lumefantrine (AL+). Recurrent vivax infections were treated with chloroquine. Standard 12-lead electrocardiograms were assessed on day 0, 4-6 hour following the last dose and day 7.
Quinoline derivatives are considered as broad spectrum pharmacological compounds that exhibit wide range of biological activities. Integration of quinoline moiety can improve its physical and chemical properties and also pharmacological behavior. Due to its wide range of pharmaceutical applications it is very popular compound to design new drugs for treatment of multiple diseases like cancer, dengue fever, malaria, tuberculosis, fungal infections, AIDS, Alzheimer's disease and diabetes.
Malaria is a disease that requires new drugs not only to fight Plasmodium but also to reduce symptoms of infection such as fever and inflammation. A series of 21 hybrid compounds were designed from chloroquine (CQ) and primaquine (PQ) linked to the pharmacophoric group present in phenylacetic anti-inflammatory drugs. These compounds were designed to have dual activity: namely, to be capable of killing Plasmodium and still act on the inflammatory process caused by malaria infection.
The majority of the population has inappropriate malaria treatment‐seeking behavior and little is known about self‐medication practice with antimalarials among post‐partum mothers.
Malaria remains the leading cause of deaths globally, despite significant advancement towards understanding its epidemiology and availability of multiple therapeutic interventions. Poor efficacy of the approved vaccine, and the rapid emergence of antimalarial drug resistance, warrants an urgent need to expedite the process of development of new lead molecules targeting malaria.
The intrinsic fluorescence properties of two related pyrido[1,2-a]benzimidazole antimalarial compounds suitable for the cellular imaging of the human malaria parasite Plasmodium falciparum without the need to attach extrinsic fluorophores are described. Although these compounds are structurally related, they have been shown by confocal microscopy to not only accumulate selectively within P. falciparum but to also accumulate differently in the organelles investigated.
Half of the world's population lives in countries at risk of malaria infection, which results in approximately 450,000 deaths annually. Malaria parasites infect erythrocytes in a coordinated manner, with cycle durations in multiples of 24 hours, which reflects a behavior consistent with the host's circadian cycle. Interference in cycle coordination can help the immune system to naturally fight infection.