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      Developing novel anthelmintics from plant cysteine proteinases

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          Abstract

          Intestinal helminth infections of livestock and humans are predominantly controlled by treatment with three classes of synthetic drugs, but some livestock nematodes have now developed resistance to all three classes and there are signs that human hookworms are becoming less responsive to the two classes (benzimidazoles and the nicotinic acetylcholine agonists) that are licensed for treatment of humans. New anthelmintics are urgently needed, and whilst development of new synthetic drugs is ongoing, it is slow and there are no signs yet that novel compounds operating through different modes of action, will be available on the market in the current decade. The development of naturally-occurring compounds as medicines for human use and for treatment of animals is fraught with problems. In this paper we review the current status of cysteine proteinases from fruits and protective plant latices as novel anthelmintics, we consider some of the problems inherent in taking laboratory findings and those derived from folk-medicine to the market and we suggest that there is a wealth of new compounds still to be discovered that could be harvested to benefit humans and livestock.

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          Most cited references108

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          Control of neglected tropical diseases.

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            Drug resistance in nematodes of veterinary importance: a status report.

            Ray Kaplan (2004)
            Reports of drug resistance have been made in every livestock host and to every anthelmintic class. In some regions of world, the extremely high prevalence of multi-drug resistance (MDR) in nematodes of sheep and goats threatens the viability of small-ruminant industries. Resistance in nematodes of horses and cattle has not yet reached the levels seen in small ruminants, but evidence suggests that the problems of resistance, including MDR worms, are also increasing in these hosts. There is an urgent need to develop both novel non-chemical approaches for parasite control and molecular assays capable of detecting resistant worms.
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              A new class of anthelmintics effective against drug-resistant nematodes.

              Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics--the benzimidazoles, imidazothiazoles and macrocyclic lactones--has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.
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                Author and article information

                Journal
                Parasit Vectors
                Parasites & Vectors
                BioMed Central
                1756-3305
                2008
                1 September 2008
                : 1
                : 29
                Affiliations
                [1 ]School of Biology, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
                [2 ]Academic Unit of Molecular Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
                [3 ]Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, G61 1QH, UK
                Article
                1756-3305-1-29
                10.1186/1756-3305-1-29
                2559997
                18761736
                190bd388-3780-44ce-96ad-26bfe670259c
                Copyright © 2008 Behnke et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 July 2008
                : 1 September 2008
                Categories
                Review

                Parasitology
                Parasitology

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