Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes.

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Robinson SJ, Hoobler EK, Riener M, Loveridge ST, Tenney K, Valeriote FA, Holman TR, Crews P

Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes.

J Nat Prod. 2009 Oct;72(10):1857-63. doi: 10.1021/np900465e.

PubMed ID
19848434 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
MasoprocolArachidonate 5-lipoxygenaseIC 50 (nM)110N/AN/ADetails
ZileutonArachidonate 5-lipoxygenaseIC 50 (nM)500N/AN/ADetails