In Vitro Activities of 25 Quinolones and Fluoroquinolones against Liver and Blood Stage
            <i>Plasmodium</i>
            spp

Mahmoudi, Nassira; Ciceron, Liliane; Franetich, Jean‐François; Farhati, Khemais; Silvie, Olivier; Eling, W.M.C.; Sauerwein, Robert W.; Danis, M.; Mazier, Dominique; Derouin, Francis

doi:10.1128/aac.47.8.2636-2639.2003

Cited by 80 publications

(75 citation statements)

References 20 publications

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“…The sporozoite development within the hepatocyte into a schizont stage is followed either by Giemsa staining or immunofluorescence assay using specific antibodies or a genetically-manipulated fluorescent parasite. Potential antimalarial drugs acting on the hepatic stage have emerged (Carraz et al, 2006, Mahmoudi et al, 2003, Mahmoudi et al, 2008, Parvanova et al, 2009, Singh et al, 2010, Tasdemir et al, 2010, Yu et al, 2008. A high-throughput in vitro screening of drug activity on Plasmodium liver stages was developed based on a sophisticated infrared fluorescence scanning system, which allows rapid, automatic counting of infected hepatocytes (Gego et al, 2006).…”

Section: Bioassays For the Hepatic Stage Of Plasmodiummentioning

confidence: 99%

Advances in Antimalarial Drug Evaluation and New Targets for Antimalarials

Grellier¹,

Deregnaucourt²,

Isabelle³

2012

Malaria Parasites

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Section: Bioassays For the Hepatic Stage Of Plasmodiummentioning

confidence: 99%

Advances in Antimalarial Drug Evaluation and New Targets for Antimalarials

Grellier¹,

Deregnaucourt²,

Isabelle³

2012

Malaria Parasites

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“…The identification of new drugs is slowed down by the lack of a reliable and sensitive method allowing a high-throughput screening. In vitro drug sensitivity assays are largely based on evaluating the number of liver schizonts in sporozoite-infected cultures (7,10,15). Even if alternative methods have been proposed (6), the number of infected cells is usually determined by microscopy analysis.…”

mentioning

confidence: 99%

New Approach for High-Throughput Screening of Drug Activity onPlasmodiumLiver Stages

Gego

Silvie

Franetich

et al. 2006

Antimicrob Agents Chemother

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Plasmodium liver stages represent potential targets for antimalarial prophylactic drugs. Nevertheless, there is a lack of molecules active on these stages. We have now developed a new approach for the high-throughput screening of drug activity on Plasmodium liver stages in vitro, based on an infrared fluorescence scanning system. This method allowed us to count automatically and rapidly Plasmodium-infected hepatocytes, using different hepatic cells and different Plasmodium species, including Plasmodium falciparum. This new technique is well adapted for high-throughput drug screening and should facilitate the identification of new antimalarial compounds active on Plasmodium liver stages.Malaria remains one of the major human infectious diseases and is responsible for millions of deaths each year. As resistance to available drugs increases, there is an urgent need to identify new molecules. Targeting Plasmodium liver stage development is a valuable strategy for preventing malaria. Indeed, liver stages precede the appearance of blood stages, which are responsible for clinical symptoms and complications. The development of pharmaceutical products inhibiting the growth of Plasmodium hepatic forms is relevant for two main reasons: first, such compounds could be used as causal prophylactic agents by people exposed for a limited duration in an area where malaria is endemic (e.g., refugees and travelers) and, second, the emergence of drug-resistant strains is theoretically limited during the liver phase because of the lower parasitic load compared to the blood phase. Although hepatic stages provide attractive targets for antimalarial chemotherapy, the list of effective and widely applied drugs is still limited. The only currently available prophylactic drugs are atovaquone and two related drugs, primaquine and tafenoquine. Atovaquone has been demonstrated to be efficient on the first step of the parasite development (2); however, its use is limited by its unaffordable cost. Because of its hematological toxicity, the use of primaquine is restricted, particularly in Africa because of the frequency of G6PD deficiency (12). The identification of new drugs is slowed down by the lack of a reliable and sensitive method allowing a high-throughput screening. In vitro drug sensitivity assays are largely based on evaluating the number of liver schizonts in sporozoite-infected cultures (7, 10, 15). Even if alternative methods have been proposed (6), the number of infected cells is usually determined by microscopy analysis. Microscope-based quantification of infected cells is a very time-consuming method. Therefore, we have developed a new approach based on infrared fluorescence detection to automatically and rapidly quantify Plasmodium liver schizonts in vitro.Parasites and cells. Plasmodium berghei (ANKA strain), P. yoelii (265BY strain), and P. falciparum (NF54 strain) sporozoites were obtained from dissection of infected Anopheles stephensi mosquito salivary glands. Human hepatocarcinoma HepG2-A16 cells were cultured in Dulbecco ...

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“…Mantel-Cox logrank c 8ϳ16 week old Swiss mice (Charles Rivers, Orleans, France). They were isolated from the tissues by collagenase perfusion as previously described [11,12] then resuspended in William's medium (Gibco, Cergy-Pontoise, France) supplemented to a final concentration of 10% fetal calf serum (Gibco), 2% penicillin -streptomycin, 1% sodium pyruvate, 1% L-glutamine, 1% insulin -transferrin -selenium, at 37°C in 4% CO 2 . Eighty thousand mouse hepatocytes were seeded in each well allowing cell confluence.…”

Section: Plasmodium Yoelii Yoeliimentioning

confidence: 99%

“…Slides were then fixed in cold methanol for 10 minutes, then incubated for 1 hour at 37°C with a polyclonal antibody directed against the heat shock protein of Plasmodium (HSPi72) at a dilution of 1/500 [11,12]. The slides were then washed in phosphate-buffered saline (PBS) and incubated for 1 hour at 37°C with a solution containing an anti-mouse IgG FITC conjugate (Sigma) diluted at 1/500, with 4Ј,6-diamidino-2-phenyindole (DAPI) (Sigma) diluted at 1/1000 and Evans Blue (Sigma) at 1/150000.…”

Section: Plasmodium Yoelii Yoeliimentioning

confidence: 99%

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Antimalarial Activity of Crambescidin 800 and Synthetic Analogues against Liver and Blood Stage of Plasmodium sp.

et al. 2006

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Structural features associated with the antimalarial activity of the marine natural product crambescidin 800 were studied using synthetic analogues of the related compound ptilomycalin A. The study suggests that the guanidine moiety is cytotoxic, whereas the spermidine-containing aliphatic chain increases activity. The most active analogue, compound 11, had in vitro activity against Plasmodium falciparum strain 3D7 (IC 50 ϭ490 nM) that was stronger than the in vitro activity against murine L5178Y cells (IC 50 ϭ8.5ϳ59 mM). In vitro growth inhibition of liver stages of P. yoelii yoelii in mouse hepatocytes was observed (IC 50 ϭ9.2 mM). The compound did not significantly prolong median survival time after a single subcutaneous administration of 80 mg/kg in P. berghei-infected mice. Compound 11 did not cause DNA fragmentation in an in vitro micronucleus assay. Keywords malaria, natural product, crambescidin, Plasmodium DescriptionCrambescidin 800 was isolated from a Mycophora sp. sponge. The methanol extract was partitioned with hexane, dichloromethane (DCM) and chloroform. The DCM fraction was chromatographed successively on Sephadex LH20 (101.6ϫ2.5 cm, 100% methanol, 2 ml/minute, elution volume (V e )ϭ280 ml) and C18 columns (gravity column, 50.8ϫ2.5 cm, methanol/water 9 : 1, 1 ml/minute, V e ϭ33 ml) yielding a bioactive fraction (55.4 mg) whose 1 H-and 13 C-NMR shifts and mass spectrum data matched previously reported values for crambescidin 800 [1].Analogues had been synthesized as described and were provided (by P. J. Murphy) as pure crystalline solids [2ϳ5]. The structures are shown in Fig. 1.The structures of crambescidin 800, ptilomycalin A, and the synthetic compound 11 are shown in Fig. 2.

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In Vitro Activities of 25 Quinolones and Fluoroquinolones against Liver and Blood Stage Plasmodium spp

Cited by 80 publications

References 20 publications

Advances in Antimalarial Drug Evaluation and New Targets for Antimalarials

Advances in Antimalarial Drug Evaluation and New Targets for Antimalarials

New Approach for High-Throughput Screening of Drug Activity onPlasmodiumLiver Stages

Antimalarial Activity of Crambescidin 800 and Synthetic Analogues against Liver and Blood Stage of Plasmodium sp.

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