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      Effect of Antimalarial Drugs on Plasmodia Cell-Free Protein Synthesis

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          Abstract

          A cell-free system from Plasmodium falciparum able to translate endogenous mRNA was used to determine the effect of artemisinin, chloroquine and primaquine on the protein synthesis mechanism of the parasite. The antimalarial drugs did not inhibit the incorporation of [³H] methionine into parasite proteins even at concentrations higher than the ones found to strongly inhibit the parasite growth. Results clearly indicate that these compounds do not have a direct effect on protein synthesis activity of P. falciparum coded by endogenous mRNA.

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          Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4

          U K Laemmli (1970)
          Article 0 comments Cited 3800 times – based on 0 reviews     Review now
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            Human malaria parasites in continuous culture

            W Trager, J. J. Jensen (1976)
            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 (1 or 5 percent). The original parasite material, derived from an infected Aotus trivirgatus monkey, was diluted more than 100 million times by the addition of human erythrocytes at 3- or 4-day intervals. The parasites continued to reproduce in their normal asexual cycle of approximately 48 hours but were no longer highly synchronous. The have remained infective to Aotus.
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              Plasmodium falciparum: in vitro studies of the pharmacodynamic properties of drugs used for the treatment of severe malaria.

              Cajo ter Braak, P Holloway, Uma S. Krishna … (1993)
              The speed and stage specificity of antimalarial drug action on the metabolic activities of cultured Plasmodium falciparum were studied for chloroquine (CQ), quinine (QN), artemisinin (AR), and sodium artelinate (SA). CQ had the most rapid onset of action on [3H]hypoxanthine and [3H]isoleucine uptake, reaching 50% of its maximum effect in 1.8 hr compared with 3.5-7.4 hr for the other three drugs. In contrast there was a lag time of 1-4 hr before AR and SA had a measurable inhibitory effect, although after this delay antimalarial action was very rapid. Parasite glycolysis was relatively drug resistant; the inhibition of lactate production was < 60% of that for [3H]hypoxanthine and [3H]isoleucine uptake. The susceptibility of P. falciparum changed markedly as the parasite matured. Maximum drug effects occurred at the late ring and early trophozoite stage, which corresponds to the time at which the most rapid increases in synthetic and glycolytic activities occur. Mature schizonts and young rings were relatively unaffected by the antimalarial drugs. Young rings were particularly resistant to QN. Schizonts multiplied successfully in the presence of relatively high concentrations of all four drugs. The two artemisinin compounds had the broadest time window of action and may be particularly suitable for the treatment of severe malaria.
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                Author and article information

                Journal
                Journal ID (publisher-id): mioc
                Title: Memórias do Instituto Oswaldo Cruz
                Abbreviated Title: Mem. Inst. Oswaldo Cruz
                Publisher: Instituto Oswaldo Cruz, Ministério da Saúde (Rio de Janeiro, RJ, Brazil )
                ISSN (Print): 0074-0276
                ISSN (Electronic): 1678-8060
                Publication date (Print and electronic): April 2002
                Volume: 97
                Issue: 3
                Pages: 377-380
                Affiliations
                [01] Aragua orgnameUniversidad de Carabobo-Núcleo Aragua orgdiv1Facultad de Ciencias de la Salud orgdiv2Centro de Investigaciones Biomédicas Venezuela
                Article
                Publisher ID: S0074-02762002000300018 Publisher ID: S0074-0276(02)09700318
                DOI: 10.1590/S0074-02762002000300018
                SO-VID: 1cde4179-dad2-45e8-a039-9079e62e06b9
                License:

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                Date received : 09 March 2001
                Date accepted : 12 December 2001
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 21, Pages: 4
                Product

                SciELO Brazil

                Categories
                Subject: Experimental Chemotherapy

                Keywords: antimalarial drugs,Plasmodium falciparum,protein synthesis,cell free translation
                Data availability:
                Keywords: antimalarial drugs, Plasmodium falciparum, protein synthesis, cell free translation

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