Inhibition of efflux of quinolines as new therapeutic strategy in malaria.

  title={Inhibition of efflux of quinolines as new therapeutic strategy in malaria.},
  author={Maud Henry and Sandrine Alibert and Christophe Rogier and Jacques Barbe and Bruno Pradines},
  journal={Current topics in medicinal chemistry},
  volume={8 7},
Plasmodium falciparum is one of the most lethal parasite responsible for human malaria. Until now, the only one solution to counter malaria is the use of antimalarial drugs. Unfortunately, the extensively use of drugs, such as quinolines (i.e. chloroquine, quinine or mefloquine), have led to the emergence of drug resistance. Chloroquine and probably other quinolines act in interfering in the detoxification of hematin in the digestive vacuole. Quinolines are accumulated in P. falciparum… 

Plasmodium falciparum Multidrug Resistance Proteins (pfMRPs)

MRPs (Multidrug Resistance Protein) are associated with in vivo and in vitro altered drug response, and might be important factors for the development of multi-drug resistance phenotypes, a latent possibility in the present, and future, combination therapy environment.

Antimalarial drugs: modes of action and mechanisms of parasite resistance.

Recent progress in tackling the problem of parasite resistance is summarized and the underlying molecular mechanisms that confer resistance to current antimalarial agents as far as they are known are discussed, understanding of which should assist in the rational development of new drugs and the more effective deployment of older ones.

Efficacy of Lumefantrine against piperaquine resistant Plasmodium berghei parasites is selectively restored by probenecid, verapamil, and cyproheptadine through ferredoxin NADP+-reductase and cysteine desulfurase

It is demonstrated that the incorporation of any of the RA into an antimalarial combination that comprises LM would augment LM activity and concomitantly antagonize the emergence of LM resistance derived from PQ pressure, and clues on the link between SUFS and FNR are provided.

Atorvastatin as a potential anti-malarial drug: in vitro synergy in combinational therapy with quinine against Plasmodium falciparum

The synergistic effect of AVA in combination with QN was found to be unrelated to mutations occurring in transport protein genes involved in QN drug resistance, suggesting that AVA will be a good candidate for combinatorial malaria treatment.

Antimalarial application of quinones: A recent update.

Overcoming chloroquine resistance in malaria: Design, synthesis and structure-activity relationships of novel chemoreversal agents.

Atorvastatin Is a Promising Partner for Antimalarial Drugs in Treatment of Plasmodium falciparum Malaria

ABSTRACT Atorvastatin (AVA) is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. AVA exposure resulted in the reduced in vitro growth of 22 Plasmodium falciparum strains, with the 50%

A Whole Cell Pathway Screen Reveals Seven Novel Chemosensitizers to Combat Chloroquine Resistant Malaria

A simple and direct means to rapidly screen for resistance-conferring mutations in chloroquine using a fluorescent-tagged CQ molecule and two which showed greater potency than the classical chemosensitizers verapamil and desipramine are proposed.

Novel C11 amino derivatives of cryptolepine : synthesis and in vitro studies with DNA and haeme

A series of quindolones derivatives, targeting malaria parasite digestive vacuole and haeme detoxification pathway, are synthesized through the incorporation of basic side-chains in the C-11 position of the 10H-indolo[3,2-b]quinolin-11-one (quindolone) scaffold and evaluated for their antiplasmodial and cytotoxicity properties.

Prevalence of molecular markers of Plasmodium falciparum drug resistance in Dakar, Senegal

To estimate the prevalence of resistance to several anti-malarial drugs since the introduction of the widespread use of ACT, the presence of molecular markers associated with resistance to chloroquine and sulphadoxine-pyrimethamine was assessed in local isolates at the military hospital of Dakar.