Antimalarial activity of pyrroloiminoquinones from the Australian marine sponge Zyzzya sp.
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).
Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia.
Rohan A
RA
Davis
Malcolm S
MS
Buchanan
Sandra
S
Duffy
Vicky M
VM
Avery
Susan A
SA
Charman
William N
WN
Charman
Karen L
KL
White
David M
DM
Shackleford
Michael D
MD
Edstein
Katherine T
KT
Andrews
David
D
Camp
Ronald J
RJ
Quinn
D000818:Animals; D000962:Antimalarials / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects; D011161:Porifera / Q000737:chemistry*; D047608:Pyrroloiminoquinones / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity
D000962:Antimalarials; D047608:Pyrroloiminoquinones