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Amazonian Plant Natural Products: Perspectives for Discovery of New Antimalarial Drug Leads
Instituto Nacional de Pesquisa da Amazônia (INPA), Av. André Araújo, 2936, 69067-375 Manaus, AM, Brazil
Departamento de Genética, Evolução e Bioagentes, Universidade Estadual de Campinas-UNICAMP, P.O. Box 6109, 13083-862 Campinas, SP, Brazil
Laboratório Nacional de Biociências (LNBio) – Centro Nacional de Pesquisa em Energia e Materiais (CNEPM) - P.O. Box 6192, 13083-970 Campinas, SP, Brazil
Programa de Mestrado em Sociedade, Tecnologia e Meio Ambiente. UniEVANGÉLICA-Centro Universitário de Anápolis, 75083-515 Anapólis, GO, Brazil
Centro de Malária e Doenças Tropicais, LA/IHMT-Universidade Nova de Lisboa, 1349-008 Lisboa, Portugal
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, 69040-000 Manaus, AM, Brazil
Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, 69040-000 Manaus, AM, Brazil
* Authors to whom correspondence should be addressed.
Received: 2 July 2013; in revised form: 14 July 2013 / Accepted: 18 July 2013 / Published: 2 August 2013
Abstract: Plasmodium falciparum and P. vivax malaria parasites are now resistant, or showing signs of resistance, to most drugs used in therapy. Novel chemical entities that exhibit new mechanisms of antiplasmodial action are needed. New antimalarials that block transmission of Plasmodium spp. from humans to Anopheles mosquito vectors are key to malaria eradication efforts. Although P. vivax causes a considerable number of malaria cases, its importance has for long been neglected. Vivax malaria can cause severe manifestations and death; hence there is a need for P. vivax-directed research. Plants used in traditional medicine, namely Artemisia annua and Cinchona spp. are the sources of the antimalarial natural products artemisinin and quinine, respectively. Based on these compounds, semi-synthetic artemisinin-derivatives and synthetic quinoline antimalarials have been developed and are the most important drugs in the current therapeutic arsenal for combating malaria. In the Amazon region, where P. vivax predominates, there is a local tradition of using plant-derived preparations to treat malaria. Here, we review the current P. falciparum and P. vivax drug-sensitivity assays, focusing on challenges and perspectives of drug discovery for P. vivax, including tests against hypnozoites. We also present the latest findings of our group and others on the antiplasmodial and antimalarial chemical components from Amazonian plants that may be potential drug leads against malaria.
Keywords: herbal remedy; Plasmodium spp.; antimalarials; drug discovery; Amazonian plants
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Pohlit, A.M.; Lima, R.B.S.; Frausin, G.; Silva, L.F.R.; Lopes, S.C.P.; Moraes, C.B.; Cravo, P.; Lacerda, M.V.G.; Siqueira, A.M.; Freitas-Junior, L.H.; Costa, F.T.M. Amazonian Plant Natural Products: Perspectives for Discovery of New Antimalarial Drug Leads. Molecules 2013, 18, 9219-9240.
Pohlit AM, Lima RBS, Frausin G, Silva LFR, Lopes SCP, Moraes CB, Cravo P, Lacerda MVG, Siqueira AM, Freitas-Junior LH, Costa FTM. Amazonian Plant Natural Products: Perspectives for Discovery of New Antimalarial Drug Leads. Molecules. 2013; 18(8):9219-9240.
Pohlit, Adrian M.; Lima, Renata B.S.; Frausin, Gina; Silva, Luiz F.R.; Lopes, Stefanie C.P.; Moraes, Carolina B.; Cravo, Pedro; Lacerda, Marcus V.G.; Siqueira, André M.; Freitas-Junior, Lucio H.; Costa, Fabio T.M. 2013. "Amazonian Plant Natural Products: Perspectives for Discovery of New Antimalarial Drug Leads." Molecules 18, no. 8: 9219-9240.