期刊
MARINE DRUGS
卷 8, 期 3, 页码 429-437出版社
MDPI
DOI: 10.3390/md8030429
关键词
nitric oxide production; norsesterterpene peroxide; Latrunculia sp.; RAW 264.7 Cells
资金
- Cancer Research Center Hawaii
- College of Pharmacy
- National Cancer Institute [P01 CA48112]
Seven norsesterterpene peroxides: epimuqubilin A (1), muqubilone B (2), unnamed cyclic peroxide ester (3), epimuqubilin B (4), sigmosceptrellin A methyl ester (5), sigmosceptrellin A (6), and sigmosceptrellin B methyl ester (7), isolated from the marine sponge Latrunculia sp., were examined with regard to their effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells. The results indicated epimuqubilin A (1) possessed potent NO inhibitory activity against lipopolysaccharide (LPS)-induced nitric oxide release with an IC50 value of 7.4 mu M, a level three times greater than the positive control, L-N-G-monomethyl arginine citrate, followed by 6 (sigmosceptrellin A, IC50 = 9.9 mu M), whereas other compounds exhibited only modest activity (Table 1). These compounds did not show appreciable cytotoxicity at their IC50 values for NO-inhibitory activity. The structure-activity upon NO inhibition could be summarized as follows: (1) a monocyclic carbon skeleton framework was essential for activity, (2) free acids gave higher activity, (3) the orientation of H-3-22 with an equatorial position increased activity, and (4) a bicyclic structure reduced activity. This is the first report of a norsesterterpene peroxide with NO-inhibitory activity. In addition, compounds 1-7 were also evaluated for their inhibitory activities in the yeast glycogen synthase kinase-3 beta assay. In summary, several norsesterterpene peroxides showed novel biological activities of inhibition in NO production, suggesting that these might provide leads for anti-inflammatory or cancer chemopreventive agents.
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