Antimalarial drug discovery — approaches and progress towards new medicines

Cell-Cell Communication between Malaria-Infected Red Blood Cells via Exosome-like Vesicles

(2013) Neta Regev-Rudzki et al.   CELL

Na+ Regulation in the Malaria Parasite Plasmodium falciparum Involves the Cation ATPase PfATP4 and Is a Target of the Spiroindolone Antimalarials

(2013) Natalie J. Spillman et al.   Cell Host & Microbe

Malaria-Infected Erythrocyte-Derived Microvesicles Mediate Cellular Communication within the Parasite Population and with the Host Immune System

(2013) Pierre-Yves Mantel et al.   Cell Host & Microbe

Human Infections and Detection of Plasmodium knowlesi

(2013) B. Singh et al.   CLINICAL MICROBIOLOGY REVIEWS

A Plasmodium falciparum screening assay for anti-gametocyte drugs based on parasite lactate dehydrogenase detection

(2013) Sarah D'Alessandro et al.   JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY

Comparative Antimalarial Activities and ADME Profiles of Ozonides (1,2,4-trioxolanes) OZ277, OZ439, and Their 1,2-Dioxolane, 1,2,4-Trioxane, and 1,2,4,5-Tetraoxane Isosteres

(2013) Xiaofang Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Creative solutions to extraordinary challenges in clinical trials: methodology of a phase III trial of azithromycin and chloroquine fixed-dose combination in pregnant women in Africa

(2013) Richa S Chandra et al.   MALARIA JOURNAL

Designing the next generation of medicines for malaria control and eradication

(2013) Jeremy N Burrows et al.   MALARIA JOURNAL

Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia

(2013) Olivo Miotto et al.   NATURE GENETICS

Immune mechanisms in malaria: new insights in vaccine development

(2013) Eleanor M Riley et al.   NATURE MEDICINE

Beyond insecticides: new thinking on an ancient problem

(2013) Elizabeth A. McGraw et al.   NATURE REVIEWS MICROBIOLOGY

Qualification of Standard Membrane-Feeding Assay with Plasmodium falciparum Malaria and Potential Improvements for Future Assays

(2013) Kazutoyo Miura et al.   PLoS One

Torins are potent antimalarials that block replenishment of Plasmodium liver stage parasitophorous vacuole membrane proteins

(2013) K. K. Hanson et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Wolbachia Invades Anopheles stephensi Populations and Induces Refractoriness to Plasmodium Infection

(2013) G. Bian et al.   SCIENCE

Quinolone-3-Diarylethers: A New Class of Antimalarial Drug

(2013) A. Nilsen et al.   Science Translational Medicine

Development and Optimization of a Novel 384-Well Anti-Malarial Imaging Assay Validated for High-Throughput Screening

(2012) Sandra Duffy et al.   AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE

The Spiroindolone Drug Candidate NITD609 Potently Inhibits Gametocytogenesis and Blocks Plasmodium falciparum Transmission to Anopheles Mosquito Vector

(2012) J. C. van Pelt-Koops et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

A Class of Tricyclic Compounds Blocking Malaria Parasite Oocyst Development and Transmission

(2012) Richard T. Eastman et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

First-in-man safety and pharmacokinetics of synthetic ozonide OZ439 demonstrates an improved exposure profile relative to other peroxide antimalarials

(2012) Joerg J. Moehrle et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Selective and Specific Inhibition of the Plasmodium falciparum Lysyl-tRNA Synthetase by the Fungal Secondary Metabolite Cladosporin

(2012) Dominic Hoepfner et al.   Cell Host & Microbe

Global Phenotypic Screening for Antimalarials

(2012) W. Armand Guiguemde et al.   CHEMISTRY & BIOLOGY

Characterization of Plasmodium Liver Stage Inhibition by Halofuginone

(2012) Emily R. Derbyshire et al.   ChemMedChem

Relapse of imported vivax malaria despite standard-dose primaquine therapy: an investigation with molecular genotyping analyses

(2012) T.-Y. Chiang et al.   CLINICAL MICROBIOLOGY AND INFECTION

Dihydroartemisinin/Piperaquine

(2012) Gillian M. Keating   DRUGS

Ketotifen is an antimalarial prodrug of norketotifen with blood schizonticidal and liver-stage efficacy

(2012) Erin Milner et al.   EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS

Whole-cellin vitroscreening for gametocytocidal compounds

(2012) Leonardo Lucantoni et al.   Future Medicinal Chemistry

A high-throughput assay for the identification of malarial transmission-blocking drugs and vaccines

(2012) Michael J. Delves et al.   INTERNATIONAL JOURNAL FOR PARASITOLOGY

Measuring the blockade of malaria transmission – An analysis of the Standard Membrane Feeding Assay

(2012) Thomas S. Churcher et al.   INTERNATIONAL JOURNAL FOR PARASITOLOGY

Drug Screen Targeted at Plasmodium Liver Stages Identifies a Potent Multistage Antimalarial Drug

(2012) Filipa P. da Cruz et al.   JOURNAL OF INFECTIOUS DISEASES

3,5-Diaryl-2-aminopyridines as a Novel Class of Orally Active Antimalarials Demonstrating Single Dose Cure in Mice and Clinical Candidate Potential

(2012) Yassir Younis et al.   JOURNAL OF MEDICINAL CHEMISTRY

Imidazolopiperazines: Lead Optimization of the Second-Generation Antimalarial Agents

(2012) Advait Nagle et al.   JOURNAL OF MEDICINAL CHEMISTRY

Global malaria mortality between 1980 and 2010: a systematic analysis

(2012) Christopher JL Murray et al.   LANCET

Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study

(2012) Aung Pyae Phyo et al.   LANCET

CYP450 phenotyping and accurate mass identification of metabolites of the 8-aminoquinoline, anti-malarial drug primaquine

(2012) Brandon S Pybus et al.   MALARIA JOURNAL

The global pipeline of new medicines for the control and elimination of malaria

(2012) Melinda P Anthony et al.   MALARIA JOURNAL

ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase

(2012) Huihao Zhou et al.   NATURE

A Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Infants

(2012)   NEW ENGLAND JOURNAL OF MEDICINE

Chromatographic profiling and identification of two new iridoid-indole alkaloids by UPLC–MS and HPLC-SPE-NMR analysis of an antimalarial extract from Nauclea pobeguinii

(2012) Yong-Jiang Xu et al.   Phytochemistry Letters

Activity of Clinically Relevant Antimalarial Drugs on Plasmodium falciparum Mature Gametocytes in an ATP Bioluminescence “Transmission Blocking” Assay

(2012) Joël Lelièvre et al.   PLoS One

Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia

(2012) S. Takala-Harrison et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target

(2012) Y. Yuthavong et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Liver-stage malaria parasites vulnerable to diverse chemical scaffolds

(2012) E. R. Derbyshire et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Major Genome Region Underlying Artemisinin Resistance in Malaria

(2012) I. H. Cheeseman et al.   SCIENCE

A Divergent SAR Study Allows Optimization of a Potent 5-HT2c Inhibitor to a Promising Antimalarial Scaffold

(2012) Félix Calderón et al.   ACS Medicinal Chemistry Letters

The Activities of Current Antimalarial Drugs on the Life Cycle Stages of Plasmodium: A Comparative Study with Human and Rodent Parasites

(2012) Michael Delves et al.   PLOS MEDICINE

A Chemical Genomic Analysis of Decoquinate, aPlasmodium falciparumCytochromebInhibitor

(2011) Tae-gyu Nam et al.   ACS Chemical Biology

Cyclopropyl Carboxamides, a Chemically Novel Class of Antimalarial Agents Identified in a Phenotypic Screen

(2011) Laura M. Sanz et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription

(2011) Sachel Mok et al.   BMC GENOMICS

Identification and Validation of Tetracyclic Benzothiazepines as Plasmodium falciparum Cytochrome bc1 Inhibitors

(2011) Carolyn K. Dong et al.   CHEMISTRY & BIOLOGY

The Design and Application of Target-Focused Compound Libraries

(2011) C. John Harris et al.   COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING

A High-Throughput Screen Targeting Malaria Transmission Stages Opens New Avenues for Drug Development

(2011) Kathrin Buchholz et al.   JOURNAL OF INFECTIOUS DISEASES

Imidazolopiperazines: Hit to Lead Optimization of New Antimalarial Agents

(2011) Tao Wu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies PotentPlasmodium falciparumDihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential

(2011) Jose M. Coteron et al.   JOURNAL OF MEDICINAL CHEMISTRY

Lead Optimization of Aryl and Aralkyl Amine-Based Triazolopyrimidine Inhibitors ofPlasmodium falciparumDihydroorotate Dehydrogenase with Antimalarial Activity in Mice

(2011) Ramesh Gujjar et al.   JOURNAL OF MEDICINAL CHEMISTRY

Natural products as starting points for future anti-malarial therapies: going back to our roots?

(2011) Timothy NC Wells   MALARIA JOURNAL

A high-throughput assay for the identification of drugs against late-stage Plasmodium falciparum gametocytes

(2011) Christopher L. Peatey et al.   MOLECULAR AND BIOCHEMICAL PARASITOLOGY

A malaria gametocytocidal assay using oxidoreduction indicator, alamarBlue

(2011) Takeshi Q Tanaka et al.   MOLECULAR AND BIOCHEMICAL PARASITOLOGY

How were new medicines discovered?

(2011) David C. Swinney et al.   NATURE REVIEWS DRUG DISCOVERY

Impact of high-throughput screening in biomedical research

(2011) Ricardo Macarron et al.   NATURE REVIEWS DRUG DISCOVERY

First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children

(2011)   NEW ENGLAND JOURNAL OF MEDICINE

Antimalarial Efficacy of a Quantified Extract ofNauclea pobeguiniiStem Bark in Human Adult Volunteers with Diagnosed Uncomplicated Falciparum Malaria. Part 1: A Clinical Phase IIA Trial

(2011) Kahunu Mesia et al.   PLANTA MEDICA

Towards an In Vitro Model of Plasmodium Hypnozoites Suitable for Drug Discovery

(2011) Laurent Dembele et al.   PLoS One

Plasmodium falciparum Parasites Are Killed by a Transition State Analogue of Purine Nucleoside Phosphorylase in a Primate Animal Model

(2011) María B. Cassera et al.   PLoS One

Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue

(2011) S. H. Adjalley et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Validation of isoleucine utilization targets in Plasmodium falciparum

(2011) E. S. Istvan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Artemisinin activity against Plasmodium falciparum requires hemoglobin uptake and digestion

(2011) N. Klonis et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria

(2011) S. A. Charman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Imaging of Plasmodium Liver Stages to Drive Next-Generation Antimalarial Drug Discovery

(2011) S. Meister et al.   SCIENCE

Cyclopropyl Carboxamides: A New Oral Antimalarial Series Derived from the Tres Cantos Anti-Malarial Set (TCAMS)

(2011) Lourdes Rueda et al.   ACS Medicinal Chemistry Letters

An Invitation to Open Innovation in Malaria Drug Discovery: 47 Quality Starting Points from the TCAMS

(2011) Félix Calderón et al.   ACS Medicinal Chemistry Letters

A Research Agenda to Underpin Malaria Eradication

(2011) Pedro L. Alonso et al.   PLOS MEDICINE

The Next Opportunity in Anti-Malaria Drug Discovery: The Liver Stage

(2011) Emily R. Derbyshire et al.   PLoS Pathogens

The Antimalarial Ferroquine: Role of the Metal and Intramolecular Hydrogen Bond in Activity and Resistance

(2010) Faustine Dubar et al.   ACS Chemical Biology

Identification of a 1,2,4,5-Tetraoxane Antimalarial Drug-Development Candidate (RKA 182) with Superior Properties to the Semisynthetic Artemisinins

(2010) Paul M. O'Neill et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Optimization of endochin-like quinolones for antimalarial activity

(2010) Rolf Winter et al.   EXPERIMENTAL PARASITOLOGY

Novel Inhibitors ofPlasmodium falciparumDihydroorotate Dehydrogenase with Anti-malarial Activity in the Mouse Model

(2010) Michael L. Booker et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Structure-based Design of Novel Small-Molecule Inhibitors of Plasmodium falciparum

(2010) Sandhya Kortagere et al.   Journal of Chemical Information and Modeling

Antimalarial activity and toxicity evaluation of a quantified Nauclea pobeguinii extract

(2010) Kahunu Mesia et al.   JOURNAL OF ETHNOPHARMACOLOGY

Spirotetrahydro β-Carbolines (Spiroindolones): A New Class of Potent and Orally Efficacious Compounds for the Treatment of Malaria

(2010) Bryan K. S. Yeung et al.   JOURNAL OF MEDICINAL CHEMISTRY

Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial

(2010) Antoinette K Tshefu et al.   LANCET

Identification of inhibitors for putative malaria drug targets among novel antimalarial compounds

(2010) Gregory J. Crowther et al.   MOLECULAR AND BIOCHEMICAL PARASITOLOGY

Thousands of chemical starting points for antimalarial lead identification

(2010) Francisco-Javier Gamo et al.   NATURE

Chemical genetics of Plasmodium falciparum

(2010) W. Armand Guiguemde et al.   NATURE

Speeding to a new lead

(2010) Man Tsuey Tse   NATURE REVIEWS DRUG DISCOVERY

If Artemisinin Drugs Fail, What's Plan B?

(2010) M. Enserink   SCIENCE

That Was Then But This Is Now: Malaria Research in the Time of an Eradication Agenda

(2010) S. H. I. Kappe et al.   SCIENCE

Spiroindolones, a Potent Compound Class for the Treatment of Malaria

(2010) M. Rottmann et al.   SCIENCE

The International Limits and Population at Risk of Plasmodium vivax Transmission in 2009

(2010) Carlos A. Guerra et al.   PLoS Neglected Tropical Diseases

Malaria Parasite Development in the Mosquito and Infection of the Mammalian Host

(2009) Ahmed S.I. Aly et al.   Annual Review of Microbiology

Improved Murine Model of Malaria Using Plasmodium falciparum Competent Strains and Non-Myelodepleted NOD-scid IL2R null Mice Engrafted with Human Erythrocytes

(2009) M. B. Jimenez-Diaz et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Resistance to Therapies for Infection by Plasmodium vivax

(2009) J. K. Baird   CLINICAL MICROBIOLOGY REVIEWS

The Global Portfolio of New Antimalarial Medicines Under Development

(2009) P Olliaro et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Noninvasive Real‐Time Monitoring of Liver‐Stage Development of BioluminescentPlasmodiumParasites

(2009) Agnes Mwakingwe et al.   JOURNAL OF INFECTIOUS DISEASES

Identification of a Metabolically Stable Triazolopyrimidine-Based Dihydroorotate Dehydrogenase Inhibitor with Antimalarial Activity in Mice

(2009) Ramesh Gujjar et al.   JOURNAL OF MEDICINAL CHEMISTRY

Dispersible formulation of artemether/lumefantrine: specifically developed for infants and young children

(2009) Salim Abdulla et al.   MALARIA JOURNAL

Discovery of dual function acridones as a new antimalarial chemotype

(2009) Jane X. Kelly et al.   NATURE

A pre-emptive strike against malaria's stealthy hepatic forms

(2009) Dominique Mazier et al.   NATURE REVIEWS DRUG DISCOVERY

Artemisinin Resistance inPlasmodium falciparumMalaria

(2009) Arjen M. Dondorp et al.   NEW ENGLAND JOURNAL OF MEDICINE

Argemone mexicana decoction versus artesunate-amodiaquine for the management of malaria in Mali: policy and public-health implications

(2009) Bertrand Graz et al.   TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE

Use of high-density tiling microarrays to identify mutations globally and elucidate mechanisms of drug resistance in Plasmodium falciparum

(2009) Neekesh V Dharia et al.   GENOME BIOLOGY

Antiparasitic Activities and Toxicities of Individual Enantiomers of the 8-Aminoquinoline 8-[(4-Amino-1-Methylbutyl)Amino]-6-Methoxy-4-Methyl-5-[3,4-Dichlorophenoxy]Quinoline Succinate

(2008) N. P. D. Nanayakkara et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Malaria eradication back on the table

(2008) Marcel Tanner et al.   BULLETIN OF THE WORLD HEALTH ORGANIZATION

Primaquine revisited six decades after its discovery

(2008) Nuno Vale et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Identification and Characterization of Small Molecule Inhibitors ofPlasmodium falciparumDihydroorotate Dehydrogenase

(2008) Vishal Patel et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Ferroquine, an Ingenious Antimalarial Drug –Thoughts on the Mechanism of Action

(2008) Faustine Dubar et al.   MOLECULES

In silicoactivity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen

(2008) David Plouffe et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Sex in Plasmodium: a sign of commitment

(2008) Matthew W.A. Dixon et al.   TRENDS IN PARASITOLOGY