Use este identificador para citar ou linkar para este item: http://repositorio.inpa.gov.br/handle/123/3841
Título: Comparative in vitro and in vivo antimalarial activity of the indole alkaloids ellipticine, olivacine, cryptolepine and a synthetic cryptolepine analog
Autor(es): Luiz Francisco Rocha e Silva
Andreia Montoia
Rodrigo C.N. Amorim
Márcia Rubia S Melo
Marycleuma Campos Henriques
Sergio Massayoshi Nunomura
Valter F de Andrade-Neto
D.S. Costa
G. Dantas
J. Lavrado
R. Moreira
A. Paulo
Ana Cristina Silva Pinto
R.S. Zacardi
Wanderli Pedro Tadei
Marcos Nogueira Eberlin
Adrian Martin Pohlit
Assunto: Plasmodium falciparum
Plasmodium berghei
murine macrophages
ISSN: 0944-7113
Revista: Phytomedicine (Stuttgart)
Volume: 20
Resumo: Indole alkaloids ellipticine (1), cryptolepine triflate (2a), rationally designed 11-(4-piperidinamino)cryptolepine hydrogen dichloride (2b) and olivacine (3) (an isomer of 1) were evaluated in vitro against Plasmodium falciparum and in vivo in Plasmodium berghei-infected mice. 1–3 inhibited P. falciparum (IC50 ≤ 1.4 μM, order of activity: 2b > 1 > 2a > 3). In vitro toxicity to murine macrophages was evaluated and revealed selectivity indices (SI) of 10–12 for 2a and SI > 2.8 × 102 for 1, 2b and 3. 1 administered orally at 50 mg/kg/day was highly active against P. berghei (in vivo inhibition compared to untreated control (IVI) = 100%, mean survival time (MST) > 40 days, comparable activity to chloroquine control). 1 administered orally and subcutaneously was active at 10 mg/kg/day (IVI = 70–77%; MST = 27–29 days). 3 exhibited high oral activity at ≥50 mg/kg/day (IVI = 90–97%, MST = 23–27 days). Cryptolepine (2a) administered orally and subcutaneously exhibited moderate activity at 50 mg/kg/day (IVI = 43–63%, MST = 24–25 days). At 50 mg/kg/day, 2b administered subcutaneously was lethal to infected mice (MST = 3 days) and moderately active when administered orally (IVI = 45–55%, MST = 25 days). 1 and 3 are promising compounds for development of antimalarials.
URI: http://repositorio.inpa.gov.br/handle/123/3841
ISSN: 0944-7113
DOI: https://dx.doi.org/10.1016/j.phymed.2012.09.008
Aparece nas coleções:Coordenação de Tecnologia e Inovação (COTI)

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