Drugs that kill or inhibit the sexual stages of Plasmodium could potentially amplify or synergize the impact of other interventions by blocking transmission to mosquitoes. Primaquine and other 8-aminoquinolines have long offered such potential, but safety and other concerns have limited their use. Although transmission-blocking properties are not often a priority of drug discovery efforts, a nu...

Background: The emergence and spread of chloroquine resistant Plasmodium falciparum in the world stimulated some investigators to consider different aspects of chloroquine resistance in human and rodent Plasmodia. Using animal Plasmodia, particularly primate and rodent Plasmodia can be useful model for human Plasmodia studies. In this study we have tried to consider and compare the sequence of ...

High-throughput phenotypic screening of chemical libraries has resulted in the identification of thousands of compounds with potent antimalarial activity, although in most cases, the mechanism(s) of action of these compounds remains unknown. Here we have investigated the mode of action of 90 antimalarial compounds derived from the Malaria Box collection using high-coverage, untargeted metabolom...

BACKGROUND Molecular markers for sulfadoxine-pyrimethamine (SP) resistance in Plasmodium vivax have been reported. However, data on the molecular correlates involved in the development of resistance to 4-aminoquinolines and their association with the in vivo treatment response are scarce. METHODS We assessed pvdhfr (F57L/I, S58R, T61M, S117T/N, and I173F/L) and pvmdr1 (Y976F and F1076L) mutat...

Several diaza-analogs of phenanthrene derived from 3-amino, 5-amino, 6-amino, 8-aminoquinolines, and 5-aminoisoquinoline were prepared to evaluate their antiplasmodial activities. All compounds showed mild to good activitiy in vitro, both on a Nigerian chloroquino-sensitive strain and on the chloroquino-resistant FcB1-Columbia and FcM29 strains. The position of the intracyclic nitrogen atom is ...

This report presents evidence for the interactions of several classes of cationic amphiphilic drugs including the phenothiazines, aminoquinolines, biguanides, and aromatic diamidines, with lipid A, the endotoxic principle of lipopolysaccharides. The interactions of the drugs were quantitatively assessed by fluorescence methods. The affinities of the drugs for lipid A parallel their endotoxin-an...

Since high levels of nitric oxide (NO) are implicated in neurodegenerative disorders, inhibition of the neuronal isoform of nitric oxide synthase (nNOS) and reduction of NO levels are therapeutically desirable. Nonetheless, many nNOS inhibitors mimic l-arginine and are poorly bioavailable. 2-Aminoquinoline-based scaffolds were designed with the hope that they could (a) mimic aminopyridines as p...