Antimalarial drug discovery: efficacy models for compound screening

  title={Antimalarial drug discovery: efficacy models for compound screening},
  author={David A. Fidock and Philip J. Rosenthal and Simon L. Croft and Reto Brun and Solomon Nwaka},
  journal={Nature Reviews Drug Discovery},
Increased efforts in antimalarial drug discovery are urgently needed. The goal must be to develop safe and affordable new drugs to counter the spread of malaria parasites that are resistant to existing agents. Drug efficacy, pharmacology and toxicity are important parameters in the selection of compounds for development, yet little attempt has been made to review and standardize antimalarial drug-efficacy screens. Here, we suggest different in vitro and in vivo screens for antimalarial drug… 
A structure guided drug-discovery approach towards identification of Plasmodium inhibitors
This review summarizes the work undertaken by different scientific groups over the last five years to develop inhibitors from natural, semisynthetic or synthetic sources, which will be valuable to medicinal chemists to develop novel antimalarial agents.
Antimalarial drug development: past to present scenario.
An overview of past to present status of antimalarial drugs including newly researched candidates and also the alternative approaches for the complete control of malaria are presented.
Novel approaches in antimalarial drug discovery
The classical and new approaches to antimalarial drug discovery are reviewed, with a special emphasis on the various stages of the parasite's life cycle and the different Plasmodium species.
Screening of antimalarial drugs: An overview
This review is an update of various conventional and latest in vitro and in vivo screening methods being used for evaluation of antimalarial compounds.
4-aminoquinolines: An Overview of Antimalarial Chemotherapy
The recent developments in 4-aminoquinoline derived new analogs and insight into design and development of new antimalarials are discussed.
A New In Vivo Screening Paradigm to Accelerate Antimalarial Drug Discovery
A global multilateral collaborative project aimed at screening the significant chemical diversity within the antimalarial in vitro hits described in the literature is a feasible task.
Animal models of efficacy to accelerate drug discovery in malaria
An analysis of how efficacy models are used to discover new antimalarial drugs indicates that testing drug efficacy is often the last assay in each discovery stage and the experimental designs utilized are not optimized to expedite decision-making and inform clinical development.
Development in Assay Methods for in Vitro Antimalarial Drug Efficacy Testing: A Systematic Review
The basic necessity behind in vitro study is illustrated and how new methods are developed and subsequently adopted for high-throughput antimalarial drug screening and its application in achieving the next level of in vitro screening based on the current approaches (such as stem cells).
Falcipain inhibitors as potential therapeutics for resistant strains of malaria: a patent review
This review is focused on a selection of interesting patents published during 1999 – 2011 on peptidic and nonpeptidic chemotypes of the FP-2/FP-3 inhibitors, which could provide important insight into rational designing of FP inhibitors as potential antimalarial drugs.
Drug to genome to drug: discovery of new antiplasmodial compounds.
The structure-activity relationships, which support the hypothesis that the compounds kill the parasite via inhibition of plasmodial PDE activity, are discussed, and it is proved that antiplas modial derivatives inhibit the hydrolysis of cyclic nucleotides of the parasite, validating the cAMP/cGMP pathways as therapeutic targets against Plasmodium falciparum.


The apicoplast as an antimalarial drug target.
The recent identification of a relict chloroplast (apicoplast) in malaria and related parasites offers numerous new targets for drug therapy using well-characterized compounds.
Interactions of atovaquone with other antimalarial drugs against Plasmodium falciparum in vitro.
Proguanil emerged as the most promising of the current antimalarials as a partner for atovaquone in a fixed combination, with tetracycline as back-up.
Peptidomimetic inhibitors of protein farnesyltransferase show potent antimalarial activity.
Medical need, scientific opportunity and the drive for antimalarial drugs
Mechanisms of partnering with industry have been established to overcome this obstacle and to open up and build on scientific opportunities for improved chemotherapy in the future.
Delaying antimalarial drug resistance with combination chemotherapy.
  • N. White
  • Biology, Medicine
  • 1999
Antimalarial drugs should not be used alone in treatment, but always in combination, as in the treatment of tuberculosis or HIV, and that the combination should include artemisinin or one of its derivatives.
Monitoring antimalarial drug resistance: making the most of the tools at hand
  • C. Plowe
  • Medicine, Biology
    Journal of Experimental Biology
  • 2003
Molecular, in vitro and in vivo studies demonstrate that chloroquine-sensitive parasites reemerged and now predominate in Malawi after it switched from chloroquines to sulfadoxine/pyrimethamine, raising the intriguing possibility of rotating antimalarial drugs.
Malaria: new chemotherapeutic peroxide drugs.
Recent achievements in this area of peroxide drug development for malaria chemotherapy are summarized in this review.
Profiling drug-like properties in discovery research.
  • L. Di, E. Kerns
  • Biology, Chemistry
    Current opinion in chemical biology
  • 2003