Brief Communication | Published:

New preaustinoids from a marine-derived fungal strain Penicillium sp. SF-5497 and their inhibitory effects against PTP1B activity

Abstract

Chemical investigation of the marine-derived fungal isolate Penicillium sp. SF-5497 resulted in the isolation of two new preaustinoid-related meroterpenoids, named preaustinoid A6 (1) and preaustinoid A7 (2), along with three known metabolites (3–5). Their structures were elucidated by extensive spectroscopic analyses, such as 1D and 2D NMR and MS data. Among these, compounds 1 and 3 inhibited PTP1B activity in a dose-dependent manner, with IC50 values of 17.6 and 58.4 µM, respectively. Furthermore, kinetic analyses indicated that compound 1 inhibited PTP1B in a noncompetitive manner, with the Ki value of 17.0 µM.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  1. 1.

    Matsuda Y, Abe I. Biosynthesis of fungal meroterpenoids. Nat Prod Rep. 2016;33:26–53.

  2. 2.

    Kim D-C, et al. Dihydroisocoumarin derivatives from marine-derived fungal isolates and their anti-inflammatory effects in lipopolysaccharide-induced BV2 microglia. J Nat Prod. 2015;78:2948–55.

  3. 3.

    Park JS, et al. Furanoaustinol and 7-acetoxydehydroaustinol: new meroterpenoids from a marine-derived fungal strain Penicillium sp. SF-5497. J Antibiot. 2018;71:557–63.

  4. 4.

    Combs AP. Recent advances in the discovery of competitive protein tyrosine phosphatase 1B inhibitors for the treatment of diabetes, obesity, and cancer. J Med Chem. 2010;53:2333–44.

  5. 5.

    Bence KK, et al. Neuronal PTP1B regulates body weight, adiposity and leptin action. Nat Med. 2006;12:917–24.

  6. 6.

    Payette P, et al. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science. 1999;283:1544–8.

  7. 7.

    Zinker BA, et al. PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc Natl Acad Sci USA. 2002;99:11357–62.

  8. 8.

    dos Santos RMG, Rodrigues-Fo E. Meroterpenes from Penicillium sp. found in association with Melia azedarach. Phytochemistry. 2002;61:907–12.

  9. 9.

    dos Santos RMG, Rodrigues-Fo E. Further meroterpenes produced by Penicillium sp., an endophyte obtained from Melia azedarach. Z Naturforsch C. 2003;58c:663–9.

  10. 10.

    Duan R, et al. Antimicrobial meroterpenoids from the endophytic fungus Penicillium sp. T2-8 associated with Gastrodia elata. Phytochem Lett. 2016;18:197–201.

  11. 11.

    Gu B-B, et al. 3,5-Dimethylorsellinic acid derived meroterpenoids from Eupenicillium sp. 6A-9, a fungus isolated from the marine sponge Plakortis simplex. Eur J Org Chem. 2018;2018:48–59.

  12. 12.

    Stierle DB, et al. Berkeleyones and related meroterpenes from a deep water acid mine waste fungus that inhibit the production of interleukin 1-β from induced inflammasomes. J Nat Prod. 2011;74:2273–7.

  13. 13.

    Fill TP, Pereira GK, dos Santos RMG, Rodrigues-Fo E. Four additional meroterpenes produced by Penicillium sp. found in association with Melia azedarach. Possible biosynthetic intermediates to Austin. Z Naturforsch. 2007;62b:1035–44.

  14. 14.

    Zhang S, Zhang Z-Y. PTP1B as a drug target: recent developments in PTP1B inhibitor discovery. Drug Discov Today. 2007;12:373–81.

  15. 15.

    Jiang C-S, Liang LF, Guo Y-W. Natural products possessing protein tyrosine phosphatase 1B (PTP1B) inhibitory activity found in the last decades. Acta Pharmacol Sin. 2012;33:1217–45.

  16. 16.

    Copeland RA. Evaluation of enzyme inhibitors in drug discovery. New Jersey: John Wiley & Sons, Inc.; 2005. p. 48–81.

  17. 17.

    Wiesmann C, et al. Allosteric inhibition of protein tyrosine phosphatase 1B. Nat Struct Mol Biol. 2004;11:730–7.

  18. 18.

    Liu S, et al. Targeting inactive enzyme conformation: Aryl diketoacid derivatives as a new class of PTP1B inhibitors. J Am Chem Soc. 2008;130:17075–84.

  19. 19.

    Menna M, Imperatore C, D’Aniello F, Aiello A. Meroterpenes from marine invertebrates: structures, occurrence, and ecological implications. Mar Drugs. 2013;11:1602–43.

Download references

Acknowledgements

This research was supported by Wonkwang University in 2018.

Author information

Conflict of interest

The authors declare that they have no conflict of interest.

Correspondence to Hyuncheol Oh.

Supplementary information

  1. supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark
Fig. 1
Fig. 2