title: Amazonian plant natural products: perspectives for discovery of new antimalarial drug leads.
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.
authors.affiliation: Instituto Nacional de Pesquisa da Amazônia-INPA, Av. André Araújo 2936, 69067-375 Manaus, AM, Brazil. ampohlit@inpa.gov.br
authors.forename: Adrian Martin
authors.initials: AM
authors.lastname: Pohlit
authors.forename: Renata Braga Souza
authors.initials: RB
authors.lastname: Lima
authors.forename: Gina
authors.initials: G
authors.lastname: Frausin
authors.forename: Luiz Francisco Rocha E
authors.initials: LF
authors.lastname: Silva
authors.forename: Stefanie Costa Pinto
authors.initials: SC
authors.lastname: Lopes
authors.forename: Carolina Borsoi
authors.initials: CB
authors.lastname: Moraes
authors.forename: Pedro
authors.initials: P
authors.lastname: Cravo
authors.forename: Marcus Vinícius Guimarães
authors.initials: MV
authors.lastname: Lacerda
authors.forename: André Machado
authors.initials: AM
authors.lastname: Siqueira
authors.forename: Lucio H
authors.initials: LH
authors.lastname: Freitas-Junior
authors.forename: Fabio Trindade Maranhão
authors.initials: FT
authors.lastname: Costa
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D031172:Artemisia annua / Q000737:chemistry; D001688:Biological Products / Q000627:therapeutic use; D002738:Chloroquine / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000472:pathogenicity; D011803:Quinine / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D001688:Biological Products; D002738:Chloroquine; D011803:Quinine
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