Cytotoxic 14-Membered Macrolides from a Mangrove-Derived Endophytic Fungus, Pestalotiopsis microspora

Shuai Liu, Haofu Dai, Gamall Makhloufi, Christian Heering, Christoph Janiak, Rudolf Hartmann, Attila Mándi, T. Kurtán, Werner E G Müller, Matthias U. Kassack, Wenhan Lin, Zhen Liu, Peter Proksch

Research output: Article

34 Citations (Scopus)

Abstract

Seven new 14-membered macrolides, pestalotioprolides C (2), D-H (4-8), and 7-O-methylnigrosporolide (3), together with four known analogues, pestalotioprolide B (1), seiricuprolide (9), nigrosporolide (10), and 4,7-dihydroxy-13-tetradeca-2,5,8-trienolide (11), were isolated from the mangrove-derived endophytic fungus Pestalotiopsis microspora. Their structures were elucidated by analysis of NMR and MS data and by comparison with literature data. Single-crystal X-ray diffraction analysis was used to confirm the absolute configurations of 1, 2, and 10, while Mosher's method and the TDDFT-ECD approach were applied to determine the absolute configurations of 5 and 6. Compounds 3-6 showed significant cytotoxicity against the murine lymphoma cell line L5178Y with IC50 values of 0.7, 5.6, 3.4, and 3.9 μM, respectively, while compound 5 showed potent activity against the human ovarian cancer cell line A2780 with an IC50 value of 1.2 μM. Structure-activity relationships are discussed. Coculture of P. microspora with Streptomyces lividans caused a roughly 10-fold enhanced accumulation of compounds 5 and 6 compared to axenic fungal control.

Original languageEnglish
Pages (from-to)2332-2340
Number of pages9
JournalJournal of Natural Products
Volume79
Issue number9
DOIs
Publication statusPublished - szept. 23 2016

Fingerprint

Microsporidia
Macrolides
Fungi
Inhibitory Concentration 50
Cells
Streptomyces lividans
Cell Line
Structure-Activity Relationship
Cytotoxicity
Coculture Techniques
Human Activities
X-Ray Diffraction
Ovarian Neoplasms
X ray diffraction analysis
Lymphoma
Nuclear magnetic resonance
Single crystals

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

Liu, S., Dai, H., Makhloufi, G., Heering, C., Janiak, C., Hartmann, R., ... Proksch, P. (2016). Cytotoxic 14-Membered Macrolides from a Mangrove-Derived Endophytic Fungus, Pestalotiopsis microspora. Journal of Natural Products, 79(9), 2332-2340. https://doi.org/10.1021/acs.jnatprod.6b00473

Cytotoxic 14-Membered Macrolides from a Mangrove-Derived Endophytic Fungus, Pestalotiopsis microspora. / Liu, Shuai; Dai, Haofu; Makhloufi, Gamall; Heering, Christian; Janiak, Christoph; Hartmann, Rudolf; Mándi, Attila; Kurtán, T.; Müller, Werner E G; Kassack, Matthias U.; Lin, Wenhan; Liu, Zhen; Proksch, Peter.

In: Journal of Natural Products, Vol. 79, No. 9, 23.09.2016, p. 2332-2340.

Research output: Article

Liu, S, Dai, H, Makhloufi, G, Heering, C, Janiak, C, Hartmann, R, Mándi, A, Kurtán, T, Müller, WEG, Kassack, MU, Lin, W, Liu, Z & Proksch, P 2016, 'Cytotoxic 14-Membered Macrolides from a Mangrove-Derived Endophytic Fungus, Pestalotiopsis microspora', Journal of Natural Products, vol. 79, no. 9, pp. 2332-2340. https://doi.org/10.1021/acs.jnatprod.6b00473
Liu, Shuai ; Dai, Haofu ; Makhloufi, Gamall ; Heering, Christian ; Janiak, Christoph ; Hartmann, Rudolf ; Mándi, Attila ; Kurtán, T. ; Müller, Werner E G ; Kassack, Matthias U. ; Lin, Wenhan ; Liu, Zhen ; Proksch, Peter. / Cytotoxic 14-Membered Macrolides from a Mangrove-Derived Endophytic Fungus, Pestalotiopsis microspora. In: Journal of Natural Products. 2016 ; Vol. 79, No. 9. pp. 2332-2340.
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