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      Antiprotozoal Activities of Organic Extracts from French Marine Seaweeds

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          Abstract

          Marine macrophytes contain a variety of biologically active compounds, some reported to have antiprotozoal activity in vitro. As a part of a screening program to search for new natural antiprotozoals, we screened hydroalcoholic and ethyl acetate extracts of 20 species of seaweeds from three phyla (Rhodophyta, Heterokontophyta and Chlorophyta), sampled along the Normandy (France) coast. We tested them in vitro against the protozoa responsible for three major endemic parasitic diseases: Plasmodium falciparum, Leishmania donovani and Trypanosoma cruzi. The selectivity of the extracts was also evaluated by testing on a mammalian cell line (L6 cells). Ethyl acetate extracts were more active than hydroalcoholic ones. Activity against T. cruzi and L. donovani was non-existent to average, but almost half the extracts showed good activity against P. falciparum. The ethyl acetate extract of Mastocarpus stellatus showed the best antiplasmodial activity as well as the best selectivity index (IC 50 = 2.8 μg/mL; SI > 30). Interestingly, a red algae species, which shares phylogenetic origins with P. falciparum, showed the best antiplasmodial activity. This study is the first to report comparative antiprotozoal activity of French marine algae. Some of the species studied here have not previously been biologically evaluated.

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          Efficient technique for screening drugs for activity against Trypanosoma cruzi using parasites expressing beta-galactosidase.

          A new drug screening method was devised utilizing Trypanosoma cruzi cells that express the Escherichia coli beta-galactosidase gene. Transfected parasites catalyze a colorimetric reaction with chlorophenol red beta-D-galactopyranoside as substrate. Parasite growth in the presence of drugs in microtiter plates was quantitated with an enzyme-linked immunosorbent assay reader. The assay was performed with the mammalian form of T. cruzi that requires intracellular growth on a monolayer of fibroblast cells. To determine if selective toxicity to the parasites was occurring, the viability of the host cells in the drug was assayed with AlamarBlue. The drugs benznidazole, fluconazole, and amphotericin B were shown to inhibit the parasites at concentrations similar to those previously reported. Several compounds were tested that are inhibitors of glyceraldehyde-3-phosphate dehydrogenase of the related organisms Leishmania mexicana and Trypanosoma brucei. One of these compounds, 2-guanidino-benzimidazole, had an 50% inhibitory concentration of 10 microM in our assay. Two derivatives of this compound were identified with in vitro activity at even lower concentrations. In addition, the assay was modified for testing compounds for lytic activity against the bloodstream form of the parasite under conditions used for storing blood products. Thus, an assay with beta-galactosidase-expressing T. cruzi greatly simplifies screening drugs for selective anti-T. cruzi activity, and three promising new compounds have been identified.
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            A comparison of three methods of estimating EC50 in studies of drug resistance of malaria parasites.

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              The last man standing is the most resistant: eliminating artemisinin-resistant malaria in Cambodia

              Background Artemisinin combination therapy (ACT) is now the recommended first-line treatment for falciparum malaria throughout the world. Initiatives to eliminate malaria are critically dependent on its efficacy. There is recent worrying evidence that artemisinin resistance has arisen on the Thai-Cambodian border. Urgent containment interventions are planned and about to be executed. Mathematical modeling approaches to intervention design are now integrated into the field of malaria epidemiology and control. The use of such an approach to investigate the likely effectiveness of different containment measures with the ultimate aim of eliminating artemisinin-resistant malaria is described. Methods A population dynamic mathematical modeling framework was developed to explore the relative effectiveness of a variety of containment interventions in eliminating artemisinin-resistant malaria in western Cambodia. Results The most effective intervention to eliminate artemisinin-resistant malaria was a switch of treatment from artemisinin monotherapy to ACT (mean time to elimination 3.42 years (95% CI 3.32–3.60 years). However, with this approach it is predicted that elimination of artemisinin-resistant malaria using ACT can be achieved only by elimination of all malaria. This is because the various forms of ACT are more effective against infections with artemisinin-sensitive parasites, leaving the more resistant infections as an increasing proportion of the dwindling parasite population. Conclusion Containment of artemisinin-resistant malaria can be achieved by elimination of malaria from western Cambodia using ACT. The "last man standing" is the most resistant and thus this strategy must be sustained until elimination is truly achieved.
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                Author and article information

                Journal
                Mar Drugs
                MD
                Marine Drugs
                Molecular Diversity Preservation International
                1660-3397
                2011
                25 May 2011
                : 9
                : 6
                : 922-933
                Affiliations
                [1 ] Pharmacognosie et Molécules Naturelles Bio-actives, Laboratoire d’Innovation Thérapeutique UMR CNRS 7200, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401 Illkirch cedex, France
                [2 ] Physiologie et Ecophysiologie des Mollusques Marins, UMR M IFREMER 100, Institut de Biologie Fondamentale et Appliquée (IBFA), Université de Caen Basse-Normandie, 14032 Caen cedex, France; E-Mails: devambez@ 123456unicaen.fr (I.D.); vastarel35@ 123456hotmail.fr (A.V.); isabelle.mussio@ 123456unicaen.fr (I.M.); anne-marie.rusig@ 123456unicaen.fr (A.-M.R.)
                [3 ] Swiss Tropical and Public Health Institution, Socinstrasse 57, 4002 Basel, Switzerland; E-Mail: Marcel.Kaiser@ 123456unibas.ch
                [4 ] University of Basel, Petersplatz 1, 4003 Basel, Switzerland
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: vonthron@ 123456unistra.fr ; Tel.: +33-368-854-242; Fax: +33-368-854-311.
                Article
                marinedrugs-09-00922
                10.3390/md9060922
                3131551
                21747738
                08802c31-54cf-421f-944e-6fefb3118458
                © 2011 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 6 April 2011
                : 13 May 2011
                : 23 May 2011
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                trypanosoma,rhodophyceae,leishmania,plasmodium,phaeophyceae,seaweeds

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