Immunomodulatory Polyketides from a Phoma-like Fungus Isolated from a Soft Coral

Yi Zhe Sun, T. Kurtán, Attila Mándi, Hua Tang, Yalan Chou, Keryea Soong, Li Su, Peng Sun, Chun Lin Zhuang, Wen Zhang

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13 Citations (Scopus)

Abstract

Fourteen new polyketides with a trans-fused decalin ring system, libertalides A-N (3-16), together with two known analogues, aspermytin A and its acetate (1, 2), were isolated from the fermentation extract of a coral-derived Libertasomyces sp. fungus. Their relative configurations were elucidated on the basis of detailed spectroscopic analysis, and the absolute configurations were determined by TDDFT-ECD and optical rotation (OR) calculations. The OR of 1 and 2 were found to have opposite signs in CH3CN and CHCl3, which was in agreement with the OR calculations producing alternating signs for the optical rotation depending on the applied conditions. Because the signs of the OR for 1 and 2 showed high solvent dependence, they may not be used alone to correlate the absolute configurations. Compound 16 displayed structural novelty characterized by an α-enol ether bridge conjugated with an aldehyde group. In in vitro immunomodulatory screening, compounds 1, 4, and 10 significantly induced the proliferation of CD3+ T cells, while compounds 2, 7, 11, and 14 significantly increased the CD4+/CD8+ ratio at 3 μM. A preliminary structure-activity analysis revealed a crucial role of Δ7 and a terminal OH group in the regulation of CD3+ T cell proliferation. This is the first report of immunoregulatory activity for metabolites of this kind.

Original languageEnglish
Pages (from-to)2930-2940
Number of pages11
JournalJournal of Natural Products
Volume80
Issue number11
DOIs
Publication statusPublished - Nov 22 2017

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ASJC Scopus subject areas

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

Cite this

Sun, Y. Z., Kurtán, T., Mándi, A., Tang, H., Chou, Y., Soong, K., Su, L., Sun, P., Zhuang, C. L., & Zhang, W. (2017). Immunomodulatory Polyketides from a Phoma-like Fungus Isolated from a Soft Coral. Journal of Natural Products, 80(11), 2930-2940. https://doi.org/10.1021/acs.jnatprod.7b00463