Abstract
A new polyenyl-α-pyrone polyketide, aspopyrone A (1), was isolated from a culture broth of Okinawan plant-associated Aspergillus sp. TMPU1623 by solvent extraction, ODS column chromatography, and preparative HPLC (ODS). The structure of 1 was assigned based on NMR experiments. Compound 1 exhibited protein tyrosine phosphatase (PTP) 1B and T-cell PTP (TCPTP) inhibitory activities with IC50 values of 6.7 and 6.0 μM, respectively.
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References
Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod. 2016;79:629–61.
Demain AL, Sanchez S. Microbial drug discovery: 80 years of progress. J Antibiot. 2009;62:5–16.
Omura S. Microbial metabolites: 45 years of wandering, wondering and discovering. Tetrahedron. 2011;67:6420–59.
Butler MS, Blaskovich MA, Cooper MA. Antibiotics in the clinical pipeline at the end of 2015. J Antibiot. 2017;70:3–24.
Gunatilaka AA. Natural products from plant-associated microorganisms: distribution, structural diversity, bioactivity, and implications of their occurrence. J Nat Prod. 2006;69:509–26.
Qian S, Zhang M, He Y, Wang W, Liu S. Recent advances in the development of protein tyrosine phosphatase 1B inhibitors for type 2 diabetes. Future Med Chem. 2016;8:1239–58.
Zhang ZY, Dodd GT, Tiganis T. Protein tyrosine phosphatases in hypothalamic insulin and leptin signaling. Trends Pharmacol Sci. 2015;36:661–74.
Wang LJ, Jiang B, Wu N, Wang SY, Shi DY. Natural and semisynthetic protein tyrosine phosphatase 1B (PTP1B) inhibitors as anti-diabetic agents. RSC Adv. 2015;5:48822–34.
Jiang CS, Liang LF, Guo YW. Natural products possessing protein tyrosine phosphatase 1B (PTP1B) inhibitory activity found in the last decades. Acta Pharmacol Sin. 2012;33:1217–45.
Yamazaki H, et al. A polybromodiphenyl ether from an Indonesian marine sponge Lamellodysidea herbacea and its chemical derivatives inhibit protein tyrosine phosphatase 1B, an important target for diabetes treatment. J Nat Med. 2013;67:730–5.
Zhang YN, et al. Oleanolic acid and its derivatives: new inhibitor of protein tyrosine phosphatase 1B with cellular activities. Bioorg Med Chem. 2008;16:8697–705.
He RJ, Yu ZH, Zhang RY, Zhang ZY. Protein tyrosine phosphatases as potential therapeutic targets. Acta Pharmacol Sin. 2014;35:1227–46.
Tiganis T. PTP1B and TCPTP—nonredundant phosphatases in insulin signaling and glucose homeostasis. FEBS J. 2013;280:445–58.
Sumilat. DA, et al. Biphenyl ether derivatives with protein tyrosine phosphatase 1B inhibitory activity from the freshwater fungus Phoma sp. J Antibiot. 2017;70:331–3.
Cheng A, et al. Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. Dev Cell. 2002;2:497–503.
Zabolotny JM, et al. PTP1B regulates leptin signal transduction in vivo. Dev Cell. 2002;2:489–95.
You-Ten KE, et al. Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice. J Exp Med. 1997;186:683–93.
Heinonen KM, et al. T-cell protein tyrosine phosphatase deletion results in progressive systemic inflammatory disease. Blood. 2004;103:3457–64.
Heinonen KM, Bourdeau A, Doody KM, Tremblay ML. Protein tyrosine phosphatases PTP-1B and TC-PTP play nonredundant roles in macrophage development and IFN-γ signaling. Proc Natl Acad Sci USA. 2009;106:9368–72.
Acknowledgements
This work was supported in part by Grants-in-Aid for Scientific Research (16K21310) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan to HY and the Takeda Science Foundation to HY. We are grateful to Mr. T Matsuki and S Sato of Tohoku Medical and Pharmaceutical University for measuring mass spectra.
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Yamazaki, H., Takahashi, K., Iwakura, N. et al. A new protein tyrosine phosphatase 1B inhibitory α-pyrone-type polyketide from Okinawan plant-associated Aspergillus sp. TMPU1623. J Antibiot 71, 745–748 (2018). https://doi.org/10.1038/s41429-018-0054-y
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DOI: https://doi.org/10.1038/s41429-018-0054-y
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