Open AccessAntimalarial Activity of Pyrroloiminoquinones from the Australian Marine Sponge Zyzzya sp.
Author(s) -
Rohan A. Davis,
Malcolm S. Buchanan,
Sandra Duffy,
Vicky M. Avery,
Susan A. Charman,
William N. Charman,
Karen L. White,
David M. Shackleford,
Michael D. Edstein,
Katherine T. Andrews,
David Camp,
Ronald J. Quinn
Publication year - 2012
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/jm3002795
Subject(s) - plasmodium falciparum , sponge , chloroquine , chemistry , alkaloid , plasmodium berghei , cytotoxicity , in vitro , parasite hosting , malaria , hek 293 cells , stereochemistry , pharmacology , cell culture , biochemistry , biology , receptor , immunology , botany , world wide web , computer science , genetics
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 of >200 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).
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