Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes.
Enzyme screening of crude sponge extracts prioritized a 2005 Papua New Guinea collection of Hyrtios sp. for further study. The MeOH extract contained puupehenone and four puupehenone analogues (1, 2, 3, 5, and 7) along with a new diastereomer, 20-epi-hydroxyhaterumadienone (4), and a new analogue, 15-oxo-puupehenoic acid (6). The drimane terpene core of 4 and 6 was rapidly dereplicated, and the modified Mosher's method identified 4, while 1D and 2D NMR techniques were used to solve 6. These compounds plus noteworthy repository natural products and standards were tested against three lipoxygenase isozymes, human 5-, 12-, and 15-lipoxygenases. Significant potency and selectivity profiles were exhibited in the human 5-lipoxygenase assay by puupehenone (1) and jaspaquinol (9) and structural factors responsible for activity identified.
Robinson
Sarah J
SJ
Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California 95064, USA.
Hoobler
Eric K
EK
Riener
Michelle
M
Loveridge
Steven T
ST
Tenney
Karen
K
Valeriote
Frederick A
FA
Holman
Theodore R
TR
Crews
Phillip
P
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010219:Papua New Guinea; D011161:Porifera / Q000737:chemistry*; D012156:Reticulocytes / Q000201:enzymology; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013729:Terpenes / Q000737:chemistry; D044004:Xanthones / Q000737:chemistry* / Q000494:pharmacology*
D004224:Diterpenes; D016859:Lipoxygenase Inhibitors; D012717:Sesquiterpenes; D013729:Terpenes; D044004:Xanthones; C494670:jaspaquinol; C053594:puupehenone