Trioxaquines Are New Antimalarial Agents Active on All Erythrocytic Forms, Including Gametocytes
Françoise Benoit-Vical,Joël Lelièvre,Antoine Berry,Caroline Deymier,Odile Dechy-Cabaret,Jérôme Cazelles,Christophe Loup,Anne Robert,Jean-François Magnaval,Bernard Meunier +9 more
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TLDR
The present study confirms the absence of toxicity of this trioxaquine DU1302 on cell lines and in a mice model and exhibits potent activity against gametocytes, the form transmitted by mosquitoes, as killing of the gametocyte is essential to limit the spread of malaria.Abstract:
Malaria is the third most significant cause of infectious disease in the world. The search for new antimalarial chemotherapy has become increasingly urgent due to parasite resistance to classical drugs. Trioxaquines are synthetic hybrid molecules containing a trioxane motif (which is responsible for the antimalarial activity of artemisinin) linked to an aminoquinoline entity (which is responsible for the antiplasmodial properties of chloroquine). These trioxaquines are highly potent against young erythrocytic stages of Plasmodium falciparum and exhibit efficient activity in vitro against chloroquine-sensitive and -resistant strains of P. falciparum (50% inhibitory concentration, 4 to 32 nM) and are also active in vivo against P. vinckei petteri and P. yoelii nigeriensis in suppressive and curative murine tests. The trioxaquine DU1302 is one of these promising antimalarial agents. The present study confirms the absence of toxicity of this drug on cell lines and in a mice model. Moreover, DU1302 exhibits potent activity against gametocytes, the form transmitted by mosquitoes, as killing of the gametocytes is essential to limit the spread of malaria. The ease of chemical synthesis of this trioxaquine prototype should be considered an additional advantage and would make these drugs affordable without perturbations of the drug supply.read more
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Qinghaosu (artemisinin): the price of success.
TL;DR: Artemisinin combination treatments are now first-line drugs for uncomplicated falciparum malaria, but access to ACTs is still limited in most malaria-endemic countries and a global subsidy would make these drugs more affordable and available.
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Hybrid molecules with a dual mode of action: dream or reality?
TL;DR: In order to obtain new antimalarial drugs that are affordable and able to avoid the emergence of resistant strains, the authors developed hybrid molecules with a dual mode of action able to kill multiresistant strains by oral administration.
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Increased Tolerance to Artemisinin in Plasmodium falciparum Is Mediated by a Quiescence Mechanism
Benoit Witkowski,Joël Lelièvre,María J. López Barragán,Victor Laurent,Xin-zhuan Su,Antoine Berry,Antoine Berry,Françoise Benoit-Vical +7 more
TL;DR: In this paper, the authors showed that drug pressure could induce a subpopulation of ring stages into developmental arrest, which can explain the ART tolerance in P. falciparum.
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Next-Generation Antimalarial Drugs: Hybrid Molecules as a New Strategy in Drug Design.
Francis W. Muregi,Akira Ishih +1 more
TL;DR: This review is focused on several hybrid molecules that have been developed, with particular emphasis on those deemed to have high potential for development for clinical use.
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Concentration and purification by magnetic separation of the erythrocytic stages of all human Plasmodium species
Clotilde Ribaut,Antoine Berry,Séverine Chevalley,Karine Reybier,Isabelle Morlais,Daniel Parzy,Françoise Nepveu,Françoise Benoit-Vical,Françoise Benoit-Vical,Alexis Valentin +9 more
TL;DR: An adaptation of magnetic MACS® columns for the purification of human Plasmodium species is presented and was useful for the concentration/purification of either schizonts or gametocytes.
References
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Journal ArticleDOI
Human malaria parasites in continuous culture
William Trager,James B. Jensen +1 more
TL;DR: Plasmodium falciparum can now be maintained in continuous culture in human erythrocytes incubated at 38 degrees C in RPMI 1640 medium with human serum under an atmosphere with 7 percent carbon dioxide and low oxygen.
Journal ArticleDOI
The global distribution of clinical episodes of Plasmodium falciparum malaria
TL;DR: It is estimated that there were 515 (range 300–660) million episodes of clinical P. falciparum malaria in 2002, up to 50% higher than those reported by the World Health Organization and 200% higher for areas outside Africa, reflecting the WHO's reliance upon passive national reporting for these countries.
Journal ArticleDOI
Epidemiology of drug-resistant malaria.
TL;DR: The various features of drug resistance in Plasmodium falciparum, including its determinants, current status in diverse geographical areas, molecular markers, and their implications are described.
Journal ArticleDOI
Identification of an antimalarial synthetic trioxolane drug development candidate.
Jonathan L. Vennerstrom,Sarah Arbe-Barnes,Reto Brun,Susan A. Charman,Francis C. K. Chiu,Jacques Chollet,Yuxiang Dong,Arnulf Dorn,Daniel Hunziker,Hugues Matile,Kylie Anne McIntosh,Maniyan Padmanilayam,Josefina Santo Tomas,Christian Scheurer,Bernard Scorneaux,Yuanqing Tang,Heinrich Urwyler,Sergio Wittlin,William N. Charman +18 more
TL;DR: Here it is described how a synthetic peroxide antimalarial drug development candidate was identified in a collaborative drug discovery project.
Journal ArticleDOI
Averting a malaria disaster.
Nicholas J. White,François Nosten,Sornchai Looareesuwan,William M. Watkins,Kevin Marsh,Robert W. Snow,Gilbert Kokwaro,John H. Ouma,Tran Tinh Hien,Malcolm E. Molyneux,Malcolm E. Molyneux,Terrie E. Taylor,Terrie E. Taylor,Chris I. Newbold,TK Ruebush,M Danis,Brian Greenwood,Roy M. Anderson,Piero Olliaro +18 more
TL;DR: Pyrimethamine-sulphadoxine (PSD) is usually deployed as a successor to chloroquine, but resistance to PSD is increasing and a health calamity looms within the next few years.
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