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      The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases

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          Abstract

          Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs) affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Natural products have been a valuable source of drug regimens that form the cornerstone of modern pharmaceutical care. In this review, we highlight the potential that remains untapped in natural products as drug leads for NTDs. We cover natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of NTDs. Our coverage is limited to four major NTDs which include human African trypanosomiasis (sleeping sickness), leishmaniasis, schistosomiasis and lymphatic filariasis.

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          Most cited references254

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          Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?

          Visceral leishmaniasis (VL) is a systemic protozoan disease that is transmitted by phlebotomine sandflies. Poor and neglected populations in East Africa and the Indian sub-continent are particularly affected. Early and accurate diagnosis and treatment remain key components of VL control. In addition to improved diagnostic tests, accurate and simple tests are needed to identify treatment failures. Miltefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphotericin B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies. New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients.
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            Human African trypanosomiasis.

            Human African trypanosomiasis (sleeping sickness) occurs in sub-Saharan Africa. It is caused by the protozoan parasite Trypanosoma brucei, transmitted by tsetse flies. Almost all cases are due to Trypanosoma brucei gambiense, which is indigenous to west and central Africa. Prevalence is strongly dependent on control measures, which are often neglected during periods of political instability, thus leading to resurgence. With fewer than 12 000 cases of this disabling and fatal disease reported per year, trypanosomiasis belongs to the most neglected tropical diseases. The clinical presentation is complex, and diagnosis and treatment difficult. The available drugs are old, complicated to administer, and can cause severe adverse reactions. New diagnostic methods and safe and effective drugs are urgently needed. Vector control, to reduce the number of flies in existing foci, needs to be organised on a pan-African basis. WHO has stated that if national control programmes, international organisations, research institutes, and philanthropic partners engage in concerted action, elimination of this disease might even be possible. Copyright 2010 Elsevier Ltd. All rights reserved.
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              Qinghaosu (artemisinin): an antimalarial drug from China.

              The herb Artemisia annua has been used for many centuries in Chinese traditional medicine as a treatment for fever and malaria. In 1971, Chinese chemists isolated from the leafy portions of the plant the substance responsible for its reputed medicinal action. This compound, called qinghaosu (QHS, artemisinin), is a sesquiterpene lactone that bears a peroxide grouping and, unlike most other antimalarials, lacks a nitrogen-containing heterocyclic ring system. The compound has been used successfully in several thousand malaria patients in China, including those with both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Derivatives of QHS, such as dihydroqinghaosu, artemether, and the water-soluble sodium artesunate, appear to be more potent than QHS itself. Sodium artesunate acts rapidly in restoring to consciousness comatose patients with cerebral malaria. Thus QHS and its derivatives offer promise as a totally new class of antimalarials.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                MDPI
                1420-3049
                31 December 2016
                January 2017
                : 22
                : 1
                : 58
                Affiliations
                [1 ]Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; chkpet008@ 123456myuct.ac.za (P.M.C.); mykgod001@ 123456myuct.ac.za (G.M.)
                [2 ]Department of Pharmacology and Pharmacognosy, University of Nairobi, P.O. Box 19676, 00202 KNH Nairobi, Kenya; pckemei@ 123456gmail.com
                [3 ]Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa
                [4 ]South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa
                Author notes
                [* ]Correspondence: kelly.chibale@ 123456uct.ac.za ; Tel.: +27-21-6502553
                Article
                molecules-22-00058
                10.3390/molecules22010058
                6155950
                28042865
                4f236887-6a58-4451-84ec-d05fe02889c0
                © 2016 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 (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 December 2016
                : 27 December 2016
                Categories
                Review

                human african trypanosomiasis,leishmaniasis,schistosomiasis,lymphatic filariasis,natural products,antiprotozoal agents,phytotherapy

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