np7b00463_si_001.pdf (9.81 MB)
Immunomodulatory Polyketides from a Phoma-like Fungus Isolated from a Soft Coral
journal contribution
posted on 2017-10-19, 18:48 authored by Yi-Zhe Sun, Tibor Kurtán, Attila Mándi, Hua Tang, Yalan Chou, Keryea Soong, Li Su, Peng Sun, Chun-Lin Zhuang, Wen ZhangFourteen 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.