Bioactive γ-Lactones from the Fermented Broth of Neosartorya sp.

Abstract

Two γ-lactone derivatives, namely neosartolactone (1) and its 7-methyl ester analogue (2), have been isolated from the ethyl acetate extract of the fermented broth of Neosartorya sp. isolated in Taiwan. Structural elucidations of compounds 1 and 2 were achieved on the basis of spectroscopic analysis. Although they had been obtained via the chemical modification of avenaciolide isolated from Aspergillus avenaceus several decades ago, this is the first report to describe them from a natural resource with detailed spectroscopic interpretations. The effects of 1 and 2 on the inhibition of NO production in lipopolysaccharide (LPS)-activated murine macrophages were further evaluated. Compounds 1 and 2 significantly inhibited NO production with the IC₅₀ values of 12.2 ± 1.5 and 11.4 ± 1.0 µM, respectively; but displayed cytotoxicity at considerably higher concentrations than 50 µM.

Neosartorya - Ascomycete - mycelium - neosartolactone - iNOS

References

• 1 Hibbs Jr J B, Taintor R R, Vavrin Z. Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite.  Science. 1987;  235 473-476
• 2 Jiang J S, Shih C M, Wang S H, Chen T T, Lin C N, Ko W C. Mechanisms of suppression of nitric oxide production by 3-O-methylquercetin in RAW 264.7 cells.  J Ethnopharmacol. 2006;  103 281-287
• 3 Kleinert H, Pautz A, Linker K, Schwarz P M. Regulation of the expression of inducible nitric oxide synthase.  Eur J Pharmacol. 2004;  500 255-266
• 4 Cho H, Yun C W, Park W K, Kong J Y, Kim K S, Park Y, Lee S, Kim B K. Modulation of the acvtivity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives.  Pharmacol Res. 2004;  49 37-43
• 5 Yang S S, Wang G J, Wang S Y, Lin Y Y, Kuo Y H, Lee T H. New constituents with iNOS inhibitory activity from mycelium of Antrodia camphorata.  Planta Med. 2009;  75 512-516
• 6 Kubota T, Tsuda M, Kobayashi J. Absolute stereochemistry of amphidinolide C.  Org Lett. 2001;  3 1363-1366
• 7 Wang G J, Chen Y M, Wang T M, Lee C K, Chen K J, Lee T H. Flavonoids with iNOS inhibitory activity from Pogonatherum crinitum.  J Ethnopharmacol. 2008;  118 71-78
• 8 Brookes D, Tidd B K, Turner W B. Avenaciolide, an antifungal lactone from Aspergillus avenaceus.  J Chem Soc. 1963;  68 5385-5391
• 9 Wang G J, Chen S M, Chen W C, Chang Y M, Lee T H. Selective inducible nitric oxide synthase suppression by new bracteanolides from Murdannia bracteata.  J Ethnopharmacol. 2007;  112 221-227
• 10 Lee T H, Huang N K, Lai T C, Yang A T Y, Wang W J. Anemonin, from Clematis crassifolia, potent and selective inducible nitric oxide synthase inhibitor.  J Ethnopharmacol. 2008;  116 518-527

1 Drs. S.-S. Yang and G.-J. Wang contributed equally to this work.