Plasmodium berghei: The antimalarial action of artemisinin and sodium artelinate in vivo and in vitro, studied by flow cytometry

Vianen, P. H. Van; Klayman, Daniel L.; Lin, Ai Jeng; Lugt, C.; Engen, A.L. van; Káay, H. J. Van Der; Mons, Barend

doi:10.1016/0014-4894(90)90092-q

Cited by 38 publications

(22 citation statements)

References 10 publications

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“…However, in vivo studies using the P. bergheimouse model are needed to evaluate their potential toxicity in a mammalian host. Availability of data regarding the action of compounds 1-2 on P. berghei in vitro, will be useful to future comparison of in vivo susceptibility using the same experimental model (Vianen et al, 1990;Janse et al, 1994).…”

Section: Biological Activitymentioning

confidence: 99%

Chemical Investigation and in vitro Antimalarial Activity of Tabebuia ochracea ssp. neochrysantha

Pérez

Diaz

Medina

1997

International Journal of Pharmacognosy

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A study of Tabebuia ochracea ssp. neochrysantha, a plant traditionally used in the Amazon against malaria, was pursued. Bioactivity was tested in vitro against Plasmodium berghei and Plasmodium falciparum (FcB2 chloroquine-resistant strain). Inhibitory activity was determined by measuring parasite 3 H-hypoxanthine incorporation. Fractionation of the chloroformic extract of P. ochracea (inner stem bark) afforded five furanonaphthoquinones. The highest antimalarial activity against P. berghei was given by a mixture of two compounds which could not be separated, but the isomeric structures of 5-and 8-hydroxy-2-(1'-hydroxy)-ethylnaphtho-[2,3-b]-furan-4,9-dione ( 1 and 2) were determined from spectroscopic data. The 50% inhibitory concentration (IC 50 ) values obtained with the mixture of compounds 1 and 2 were 1.67 ϫ 10 -7 M for P. berghei and 6.77 ϫ 10 -7 for the FcB2 chloroquineresistant strain of P. falciparum. For the former parasite, the IC 50 value for chloroquine was 5 ϫ 10 -8 M. That for P. falciparum was 1.1 ϫ 10 -7 M. These results indicate that the furanonaphthoquinones isolated from T. ochracea are potential antimalarial compounds.

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Section: Biological Activitymentioning

confidence: 99%

Chemical Investigation and in vitro Antimalarial Activity of Tabebuia ochracea ssp. neochrysantha

Pérez

Diaz

Medina

1997

International Journal of Pharmacognosy

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“…In vitro tests are also useful for determining the activities of crude extracts or chromatographic fractions and for the detection and isolation of active principles [83]. Compound efficacy can be assessed by microscopic counting of the parasites, by radioactive labelling of the parasites using [3H]purine precursors, by fluorometric evaluation after staining with an appropriate dye [84 85] and by flow cytometry [86].…”

Section: Derivatives Of Artemisinin and Structureactivity Relationshipsmentioning

confidence: 99%

“…Recently, Van Vianen et al reported that the antimalarial action of sodium artelinate in vivo was slightly less than of artemisinin against synchronous cultures of P. berghei [86], by subcutaneous injection to mice. Orally administered, the action of sodium artelinate was superior to that of the injected drug.…”

Section: (5) 1990mentioning

confidence: 99%

“…A liquid preparation of sodium artesunate was more effective after transdermal administration than after an oral or a intravenous administration [152]. After oral administration of sodium artelinate, P. berghei parasites in mice were cleared from the blood with one-half to one-tenth of the dose used in parallel experiments with subcutaneous injection [86].…”

Section: (5) 1990mentioning

confidence: 99%

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Artemisia annua L.: a source of novel antimalarial drugs

Woerdenbag

Lugt²,

Pras

1990

Pharmaceutisch Weekblad Scientific Edition

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Artemisia annua L. contains artemisinin, an endoperoxide sesquiterpene lactone, mainly in its leaves and inflorescences. This compound and a series of derivatives have attracted attention because of their potential value as antimalarial drugs. In this review a survey of the currently available literature data is given. It includes phytochemical aspects, such as constituents of A. annua, the artemisinin content during the development of the plant and its biosynthesis, isolation, analysis and stability. Total chemical synthesis of artemisinin is referred to, as well as structure-activity relationships of derivatives and simplified analogues. Pharmacological studies are summarized, including the mechanism of action, interaction of the antimalarial activity with other drugs, possible occurrence of resistance to artemisinin, clinical results, toxicological aspects, metabolism and pharmacokinetics. Finally, plant cell biotechnology is mentioned as a possible means to obtain plants and cell cultures with higher artemisinin contents, allowing an industrial production of pharmaceuticals containing this novel drug.

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“…or i.v. mode, the latter being less likely to generate an immune response before the infection is fatal (20). Irrespective of the strain, P. berghei, P. chabaudi, or P. vinckei, G25 antimalarial activities obtained when parasites were i.p.…”

Section: Resultsmentioning

confidence: 99%

In Vivo Antimalarial Activities of Mono- and Bis Quaternary Ammonium Salts Interfering with Plasmodium Phospholipid Metabolism

Ancelin¹,

Calas

Bonhoure³

et al. 2003

Antimicrob Agents Chemother

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We previously showed that quaternary ammonium salts have potent antimalarial activities against the blood stage of drug-resistant Plasmodium falciparum. In the present study, 13 compounds of this series were comparatively assessed in murine in vivo malarial models. Mice infected with Plasmodium berghei were successfully treated with 11 quaternary ammonium salts in a 4-day suppressive test with a once-daily intraperitoneal administration. The dose required to decrease parasitemia by 50% (ED 50 ) ranged from 0.04 to 4.5 mg/kg of body weight. For six mono-and three bis-quaternary ammonium salts, the therapeutic indices (i.e., 50% lethal dose and ED 50 ) were higher than 5, and at best, around 20 to 30 for five of them (E6, E8, F4, G5, and G25), which is comparable to that of chloroquine under the same conditions. Plasmodium chabaudi was significantly more susceptible to G5, G15, and G25 compounds than P. berghei. Similar therapeutic indices were obtained, regardless of the administration mode or initial parasitemia (up to 11.2%). Parasitemia clearance was complete without recrudescence. Subcutaneously administered radioactive compounds had a short elimination half-life in mice (3.5 h) with low bioavailability (17.3%), which was likely due to the permanent cationic charge of the molecule. The high in vivo therapeutic index in the P. chabaudi-infected mouse model and the absence of recrudescence highlight the enormous potential of these quaternary ammonium salts for clinical malarial treatment.In the absence of vaccines, and due to the widespread resistance to antimalarials in current use, new chemotherapies are urgently needed to help in the prevention and control of malaria. The most promising strategy is to strive to discover new chemically diverse entities directed towards novel biological targets. Potential chemotherapeutic targets in the malaria parasite can be broadly classified into three categories: those involved in processes occurring in the digestive vacuole, enzymes involved in macromolecular and metabolite synthesis, and those responsible for membrane processes and signaling. The potential of putative targets to be validated will be tapped to develop effective and safe drugs (14,17,29).We previously characterized phospholipid (PL) metabolism as an attractive target for new malaria chemotherapy due to its vital importance to the parasite. PL metabolism is absent from normal mature human erythrocytes (19), but the erythrocyte PL content increases by as much as 500% after infection, specifically due to the metabolic machinery of the parasite (10, 18). Phosphatidylcholine is the major PL of infected erythrocytes, representing about 45% of the total PL. In this pathway, choline transport which regulates the supply of polar head precursors to the parasite is a regulatory rate-limiting step (3,22,23). PL polar head analogs are able to interfere with PL biosynthesis and exhibit antimalarial activity against the intraerythrocytic stage of Plasmodium falciparum in vitro (24). More particularly, 36 compounds which...

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Plasmodium berghei: The antimalarial action of artemisinin and sodium artelinate in vivo and in vitro, studied by flow cytometry

Cited by 38 publications

References 10 publications

Chemical Investigation and in vitro Antimalarial Activity of Tabebuia ochracea ssp. neochrysantha

Chemical Investigation and in vitro Antimalarial Activity of Tabebuia ochracea ssp. neochrysantha

Artemisia annua L.: a source of novel antimalarial drugs

In Vivo Antimalarial Activities of Mono- and Bis Quaternary Ammonium Salts Interfering with Plasmodium Phospholipid Metabolism

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