Gymnochromes E and F, cytotoxic phenanthroperylenequinones from a deep-water crinoid, Holopus rangii.
Bioactivity-guided fractionation of metabolites from the crinoid Holopus rangii led to the discovery of two new phenanthroperylenequinone derivatives, gymnochromes E (1) and F (2). Gymnochrome E showed cytotoxic activity toward the NCI/ADR-Res with an IC(50) of 3.5 microM. It also inhibited histone deacetylase-1 with an IC(50) of 3.3 microM. Gymnochrome F was a moderate inhibitor of myeloid cell leukemia sequence 1 (MCL-1) binding to Bak. Two anthraquinone metabolites, emodic acid (4) and its new bromo derivative (5), were also isolated from the crinoid and show remarkable similarity to the phenanthroperylenequinone core, suggesting that these metabolites share the same polyketide biosynthetic pathway.
Harbor Branch Oceanographic Institute at Florida Atlantic University, Center for Marine Biomedical and Biotechnology Research, 5600 US 1 Fort Pierce, Florida 34946, USA.
Hilaire V
HV
Kemami Wangun
Alexander
A
Wood
Catherine
C
Fiorilla
John K
JK
Reed
Peter J
PJ
McCarthy
Amy E
AE
Wright
D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004447:Echinodermata / Q000737:chemistry*; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D018942:Macrolides / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects
D000880:Anthraquinones; D000970:Antineoplastic Agents; D018942:Macrolides; C549715:gymnochrome E; C549716:gymnochrome F; D056284:Histone Deacetylase 1