MMV390048 is the first Plasmodium phosphatidylinositol 4-kinase inhibitor to reach clinical development as a new antimalarial. We aimed to characterize the safety, pharmacokinetics and antimalarial activity of a tablet formulation of MMV390048.
Malaria, one of the most striking, re‐emerging infectious diseases caused by the genus Plasmodium, places a huge burden on global healthcare systems. A major challenge in the control and eradication of malaria is the continuous emergence of increasingly widespread drug‐resistant malaria, creating an urgent need to develop novel antimalarial agents.
MMV390048 is a novel antimalarial compound that inhibits Plasmodium phosphatidylinositol-4-kinase. The safety, tolerability, pharmacokinetic profile, and antimalarial activity of MMV390048 were determined in healthy volunteers in three separate studies. A first-in-human, double-blind, randomized, placebo-controlled, single-ascending-dose study was performed. Additionally, a volunteer infection study investigated the antimalarial activity of MMV390048 using the Plasmodium falciparum induced blood-stage malaria (IBSM) model.
In spite of worldwide efforts, malaria remains one of the most devastating illnesses in the world. The huge number of lives it takes and the resistance of malaria parasites to current drugs necessitate the search for new effective antimalarial drugs. Medicinal plants have been the major source of such drugs and A. pirottae is one of these plants used traditionally for treatment of malaria in Ethiopia.
Starting from a bipyridine-sulfonamide scaffold, medicinal chemistry optimization leads to the discovery of a novel Plasmodium falciparum PI4K kinase (PfPI4K) inhibitor compound 15g (CHMFL-PI4K-127, IC50: 0.9 nM), which exhibits potent activity against 3D7 Plasmodium falciparum (P. falciparum) (EC50: 25.1 nM). CHMFL-PI4K-127 displays high selectivity against PfPI4K over human lipid and protein kinase.
Vernonia amygdalina Del. (Asteraceae) is reported to be traditionally used for the treatment of malaria. Based on folkloric repute of this plant in Ethiopian traditional medicine and crude extract-based ethnopharmacological studies conducted in few countries, this study was undertaken to evaluate the in vivo antimalarial activity of 80% methanol extract and its solvent fractions of the leaves of V. amygdalina in mice infected with Plasmodium berghei.
Hybrid molecules have the potential to enhance the efficacy against both drug-sensitive and drug-resistant organisms, and Ferroquine, a ferrocene hybrid, has demonstrated great potency in clinical trials against both drug-sensitive and drug-resistant malaria. Accordingly, hybridization of ferrocene with other antimalarial pharmacophores represents a promising strategy to develop novel antimalarial candidates.
Artefenomel and DSM265 are two new compounds that have been shown to be well tolerated and effective when administered as monotherapy malaria treatment. This study aimed to determine the safety, pharmacokinetics and pharmacodynamics of artefenomel and DSM265 administered in combination to healthy subjects in a volunteer infection study using the Plasmodium falciparum induced blood stage malaria model.