Blood schizontocidal activity of methylene blue in combination with antimalarials against<i>Plasmodium falciparum</i>

Garavito, Giovanny; Bertani, Stéphane; Rincón, Javier; Maurel, Séverine; Monje, Marie‐Carmen; Landau, I.; Valentin, Alexis; Deharo, Eric

doi:10.1051/parasite/2007142135

Cited by 29 publications

(26 citation statements)

References 30 publications

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“…Our ex vivo study presents additional evidence for NQ's potent activities against highly CQ-resistant isolates of P. falciparum and P. vivax, revealing lower IC 50 s for NQ than for all of the standard drugs with the exception of AS. The ex vivo activity of MB was greater than that of NQ, in line with previous observations in P. falciparum (19)(20)(21)(22)(23)(24)39) and P. vivax (30), with lower IC 50 s than those for all standard drugs, including AS, for both species.…”

Section: Discussionsupporting

confidence: 77%

“…The current study also confirms MB's remarkable ex vivo efficacy against resistant strains of P. falciparum and P. vivax, showing high potency, a broad stage specificity of action, including gametocyte stages (25), and synergism with other antimalarials (19,21,44). Although researchers and drug developers have been aware of the antimalarial properties of MB against P. falciparum for almost a century, it has never been widely used in clinical practice, largely due to its poor tolerability profile.…”

Section: Discussionmentioning

confidence: 49%

“…Although MB's antimalarial efficacy has been proven in several studies over the next decades, MB was abandoned from the drug development pipeline due to its low tolerability, which was the result of unpleasant, but reversible, adverse effects (18). There is renewed interest in the use of MB in the modern era of malaria therapeutics, with studies highlighting its potent schizonticidal activity against CQ-resistant P. falciparum (19)(20)(21)(22)(23)(24) and gametocytocidal activity (25)(26)(27). Furthermore, clinical trials in Africa have shown that effective antiplasmodial doses of MB are safe in both adults and children, including glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals (28,29).…”

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confidence: 99%

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Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

Wirjanata

Sebayang

Chalfein

et al. 2015

Antimicrob Agents Chemother

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fThe 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB) have potent in vitro efficacies against Plasmodium falciparum, but susceptibility data for P. vivax are limited. The species-and stage-specific ex vivo activities of NQ and MB were assessed using a modified schizont maturation assay on clinical field isolates from Papua, Indonesia, where multidrugresistant P. falciparum and P. vivax are prevalent. Both compounds were highly active against P. falciparum . Stage-specific drug susceptibility assays revealed significantly greater IC 50 s in parasites exposed at the trophozoite stage than at the ring stage for NQ in P. falciparum (26.5 versus 5.1 nM, P ‫؍‬ 0.021) and P. vivax (341.6 versus 6.5 nM, P ‫؍‬ 0.021) and for MB in P. vivax (10.1 versus 1.6 nM, P ‫؍‬ 0.010). The excellent ex vivo activities of NQ and MB against both P. falciparum and P. vivax highlight their potential utility for the treatment of multidrug-resistant malaria in areas where both species are endemic.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 49%

mentioning

confidence: 99%

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Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

Wirjanata

Sebayang

Chalfein

et al. 2015

Antimicrob Agents Chemother

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“…This quassinoid, named simalikalactone E, exhibited very good antiplasmodial activity against the three P. falciparum strains tested, whatever their geographic origin or chloroquine sensitivity. The IC 50 s obtained were in the range of most commercially available antimalarial drugs tested under similar conditions (16) Against P. falciparum gametocytes, a stage which is fundamental for transmission to mosquitoes, SkE was more active (IC 50 , 1.2 M) than the reference compound primaquine (IC 50 , 8.9 M). In a previous study, Benoit-Vical et al (3) showed that an artemisinin derivative, artesunate, inhibited gametocyte growth at a 10-fold-lower dose (around 0.1 M).…”

Section: Biodiversity Is Clearly a Source Of New Drugs (26) When Biomentioning

confidence: 73%

Antimalarial Activity of Simalikalactone E, a New Quassinoid from Quassia amara L. (Simaroubaceae)

Cachet

Ho-A-Kwie

Bertani

et al. 2009

Antimicrob Agents Chemother

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We report the isolation and identification of a new quassinoid named simalikalactone E (SkE), extracted from a widely used Amazonian antimalarial remedy made out of Quassia amara L. (Simaroubaceae) leaves. This new molecule inhibited the growth of Plasmodium falciparum cultured in vitro by 50%, in the concentration range from 24 to 68 nM, independently of the strain sensitivity to chloroquine. We also showed that this compound was able to decrease gametocytemia with a 50% inhibitory concentration sevenfold lower than that of primaquine. SkE was found to be less toxic than simalikalactone D (SkD), another antimalarial quassinoid from Q. amara, and its cytotoxicity on mammalian cells was dependent on the cell line, displaying a good selectivity index when tested on nontumorogenic cells. In vivo, SkE inhibited murine malaria growth of Plasmodium vinckei petteri by 50% at 1 and 0.5 mg/kg of body weight/day, by the oral or intraperitoneal routes, respectively. The contribution of quassinoids as a source of antimalarial molecules needs therefore to be reconsidered.This study of the antiplasmodial properties of a new quassinoid from Quassia amara L. leaves results from our ongoing work on traditional antimalarial remedies in French Guiana. Through a "knowledge, attitudes, and practices" survey focused on malaria and its treatments in this French overseas department, we showed that Q. amara leaf tea was the most frequently used antimalarial remedy (35). Q. amara belongs to the Simaroubaceae, a family known to contain quassinoids, secondary metabolites characteristic of the Sapindale order, that display a wide range of biological activities, among them antiparasitic activity and cytotoxicity (11,17).Simalikalactone D (SkD) was identified as one of the compounds responsible for the activity of Quassia amara juvenile leaf tea (6), but the small amount present in the traditional preparation, made out of mature leaves (5), could not fully explain the activity seen in vitro and in vivo (4). This is why we looked for other active ingredients responsible for the antiplasmodial activity and isolated a new quassinoid, named simalikalactone E (SkE). We report here our detailed studies of the antimalarial and cytotoxic properties of this new compound. MATERIALS AND METHODSPlant material. Leaves of Quassia amara were collected in Rémire-Montjoly, French Guiana. A sample specimen (GB3012) was deposited in the Cayenne Herbarium (CAY), and a specialist confirmed the botanical identification.Chemistry. Detailed protocol for the isolation of SkE from the aqueous decoction or the methanolic extract can be found in the supplemental material.Structural data for SkE. Structural data for simalikalactone E follow: APCIMS, 579 (MH C-30), 22.8 (C-28), 16.7 (C-20), 15.6 (C-25), 12.5 (C-29), 11.7 (C-22), 11.5 (C-27

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“…The safety and gametocytocidal activity of alternative drugs from the same family as PQ (the 8-aminoquinolines), such as bulaquine (CDRI 80/53) (162, 163) and tafenoquine (WR-238605) (99,100,371,487), require further investigation. Methylene blue, which together with quinine served as a structural starting point for the development of 8-aminoquinolines (153,406), was recently suggested as an alternative safe gametocytocidal component of drug combinations (103,531) and may be a promising gametocytocidal component of combination therapy.…”

Section: Effects Of Drugs On Gametocytemiamentioning

confidence: 99%

Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

2011

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SUMMARY Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed.

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Blood schizontocidal activity of methylene blue in combination with antimalarials againstPlasmodium falciparum

Cited by 29 publications

References 30 publications

Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

Antimalarial Activity of Simalikalactone E, a New Quassinoid from Quassia amara L. (Simaroubaceae)

Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

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