title: Antiplasmodial activity of synthetic ellipticine derivatives and an isolated analog.
abstract: Ellipticine has been shown previously to exhibit excellent in vitro antiplasmodial activity and in vivo antimalarial properties that are comparable to those of the control drug chloroquine in a mouse malaria model. Ellipticine derivatives and analogs exhibit antimalarial potential however only a few have been studied to date. Herein, ellipticine and a structural analog were isolated from Aspidosperma vargasii bark. A-ring brominated and nitrated ellipticine derivatives exhibit good in vitro inhibition of Plasmodium falciparum K1 and 3D7 strains. Several of the compounds were found not to be toxic to human fetal lung fibroblasts. 9-Nitroellipticine (IC50=0.55μM) exhibits greater antiplasmodial activity than ellipticine. These results are further evidence of the antimalarial potential of ellipticine derivatives.
authors.affiliation: National Institute for Amazon Research, Avenida André Araújo, 2936, 69067-375 Manaus, Amazonas, Brazil; Federal University of Amazonas, Avenida General Rodrigo Otávio Jordão Ramos, 3000, 69077-000 Manaus, Amazonas, Brazil.
authors.forename: Andreia
authors.initials: A
authors.lastname: Montoia
authors.affiliation: National Institute for Amazon Research, Avenida André Araújo, 2936, 69067-375 Manaus, Amazonas, Brazil; Federal University of Amazonas, Avenida General Rodrigo Otávio Jordão Ramos, 3000, 69077-000 Manaus, Amazonas, Brazil.
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Rocha E Silva
authors.affiliation: National Institute for Amazon Research, Avenida André Araújo, 2936, 69067-375 Manaus, Amazonas, Brazil.
authors.forename: Zelina E
authors.initials: ZE
authors.lastname: Torres
authors.affiliation: National Institute for Amazon Research, Avenida André Araújo, 2936, 69067-375 Manaus, Amazonas, Brazil.
authors.forename: David S
authors.initials: DS
authors.lastname: Costa
authors.affiliation: Federal University of Amazonas, Avenida General Rodrigo Otávio Jordão Ramos, 3000, 69077-000 Manaus, Amazonas, Brazil.
authors.forename: Marycleuma C
authors.initials: MC
authors.lastname: Henrique
authors.affiliation: Federal University of Amazonas, Avenida General Rodrigo Otávio Jordão Ramos, 3000, 69077-000 Manaus, Amazonas, Brazil.
authors.forename: Emerson S
authors.initials: ES
authors.lastname: Lima
authors.affiliation: Federal University of Amazonas, Avenida General Rodrigo Otávio Jordão Ramos, 3000, 69077-000 Manaus, Amazonas, Brazil.
authors.forename: Marne C
authors.initials: MC
authors.lastname: Vasconcellos
authors.affiliation: State University of Campinas, Campus Universitário Zeferino Vaz SN, 13083-970 Campinas, Brazil.
authors.forename: Rita C Z
authors.initials: RC
authors.lastname: Souza
authors.affiliation: Heitor Vieira Dourado Tropical Medicine Foundation, Avenida Pedro Teixeira, 25, 69040-000 Manaus, Amazonas, Brazil.
authors.forename: Monica R F
authors.initials: MR
authors.lastname: Costa
authors.affiliation: University of Helsinki, A.I. Virtasen aukio 1, PL 55, FI-00014 Helsinki, Finland.
authors.forename: Andriy
authors.initials: A
authors.lastname: Grafov
authors.affiliation: University of Helsinki, A.I. Virtasen aukio 1, PL 55, FI-00014 Helsinki, Finland.
authors.forename: Iryna
authors.initials: I
authors.lastname: Grafova
authors.affiliation: State University of Campinas, Campus Universitário Zeferino Vaz SN, 13083-970 Campinas, Brazil.
authors.forename: Marcos N
authors.initials: MN
authors.lastname: Eberlin
authors.affiliation: National Institute for Amazon Research, Avenida André Araújo, 2936, 69067-375 Manaus, Amazonas, Brazil.
authors.forename: Wanderli P
authors.initials: WP
authors.lastname: Tadei
authors.affiliation: National Institute for Amazon Research, Avenida André Araújo, 2936, 69067-375 Manaus, Amazonas, Brazil.
authors.forename: Rodrigo C N
authors.initials: RC
authors.lastname: Amorim
authors.affiliation: National Institute for Amazon Research, Avenida André Araújo, 2936, 69067-375 Manaus, Amazonas, Brazil. Electronic address: ampohlit@inpa.gov.br.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Pohlit
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D030009:Aspidosperma / Q000737:chemistry; D002738:Chloroquine / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D004611:Ellipticines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D004611:Ellipticines; C034192:ellipticine; D002738:Chloroquine
keywords: 2-Methyl-1,2,3,4-tetrahydroellipticine; 7,9-Dibromoellipticine; 7-Nitroellipticine; 9-Nitroellipticine; Plasmodium falciparum