Antitrypanosomal cyclic polyketide peroxides from the Australian marine sponge Plakortis sp.
Bioassay-guided fractionation of the crude extract from the Australian marine sponge Plakortis sp. led to the isolation of two new cyclic polyketide peroxides, 11,12-didehydro-13-oxo-plakortide Q (1) and 10-carboxy-11,12,13,14-tetranor-plakortide Q (2). Antitrypanosomal studies showed that compound 1 had an IC(50) value of 49 nM against Trypanosoma brucei brucei, and compound 2, where a carboxylic acid is present in the side chain, had a 20-fold reduction of activity. 11,12-Didehydro-13-oxo-plakortide Q (1) is the most active peroxide isolated so far against T. b. brucei, and it indicates the potential therapeutic value of this class of compounds.
Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia.
Yunjiang
Y
Feng
Rohan A
RA
Davis
Melissa
M
Sykes
Vicky M
VM
Avery
David
D
Camp
Ronald J
RJ
Quinn
D000818:Animals; D001315:Australia; D004146:Dioxanes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D008386:Marine Biology; D015394:Molecular Structure; D047229:Plakortis / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
C549718:10-carboxy-11,12,13,14-tetranor-plakortide Q; C549717:11,12-didehydro-13-oxo-plakortide Q; D004146:Dioxanes; D014344:Trypanocidal Agents