Antimalarial Activity of Pyrroloiminoquinones from the Australian Marine Sponge Zyzzya sp
Autor: | William N. Charman, Ronald J. Quinn, Rohan A. Davis, Malcolm Stewart Buchanan, Vicky M. Avery, Susan A. Charman, Sandra Duffy, Karen L. White, Katherine T. Andrews, David Brian Camp, Michael D. Edstein, David M. Shackleford |
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Rok vydání: | 2012 |
Předmět: |
Male
Stereochemistry Plasmodium falciparum Cell Line Antimalarials Inhibitory Concentration 50 Mice Drug Discovery Animals Humans Parasite hosting Cytotoxicity IC50 Pyrroloiminoquinones biology Chemistry Alkaloid biology.organism_classification Molecular biology In vitro Porifera Sponge Microsomes Liver Molecular Medicine |
Zdroj: | Journal of Medicinal Chemistry. 55:5851-5858 |
ISSN: | 1520-4804 0022-2623 |
DOI: | 10.1021/jm3002795 |
Popis: | A new bispyrroloiminoquinone alkaloid, tsitsikammamine C (1), displayed potent in vitro antimalarial activity with IC(50) values of 13 and 18 nM against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum, respectively. Tsitsikammamine C (1) displayed selectivity indices of200 against HEK293 cells and inhibited both ring and trophozoite stages of the malaria parasite life cycle. Previously reported compounds makaluvamines J (2), G (3), L (4), K (5) and damirones A (6) and B (7) were also isolated from the same marine sponge (Zyzzya sp.). Compounds 2-4 displayed potent growth inhibitory activity (IC(50)100 nM) against both P. falciparum lines and only moderate cytotoxicity against HEK293 cells (IC(50) = 1-4 μM). Makaluvamine G (3) was not toxic to mice and suppressed parasite growth in P. berghei infected mice following subcutaneous administration at 8 mg kg(-1) day(-1). |
Databáze: | OpenAIRE |
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