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

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 CHCN and CHCl, 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 Δ 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.

Terpenoids from the Soft Coral Sinularia sp. Collected in Yongxing Island

“…The absolute configuration of 1 was determined by time-dependent density functional theory calculation of electronic circular dichroism (TDDFT/ECD) method with the basis set RB3LYP/DGDZVP [ 12 , 13 , 14 ]. The measured ECD spectrum of 1 in methanol exhibited a negative Cotton effect (CE) at 238 nm, matching well with the calculated ECD spectra for 1a ( Figure 4 b).…”

TDDFT-ECD and DFT-NMR studies of thaigranatins A–E and granatumin L isolated fromXylocarpus granatum

“…4 Although chiroptical data of homochiral related derivatives are oen similar, a subtle change in the planar structure or substitution pattern may result in rather different [5][6][7][8] or nearly opposite ECD spectra or optical rotation. [9][10][11][12][13] TDDFT-ECD calculations of structurally related NPs having markedly different ECD spectra were found useful to interpret the differences.…”

“…Furthermore, the AC of C-6 in the side-chain of 4 remained undetermined. 16 In this work we applied DFT-NMR 13 C chemical shi calculations of the C-6 epimers to elucidate the AC of this chirality center. [27][28][29] Semi-synthetic derivatives obtained by the derivatization of granatumin L (6) showed potent human immunodeciency virus 1 (HIV-1) and inuenza A virus (IAV) inhibitory activities, which may also justify to explore relationship between stereochemistry and characteristic ECD features and to determine solution geometries and conrm the absolute conguration.…”

Cytotoxic Polyketides Isolated from the Deep-Sea-Derived Fungus Penicillium chrysogenum MCCC 3A00292

“…Structurally, versiol derivatives are classified into two types, according to the presence of a tetrahydropyran ring or not. As versiol was originally discovered from the fungus Aspergillus versicolor in 1975 [8], a total of 63 congeners have been discovered from several fungal genera [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Some of them showed interesting bioactivities, such as induced CD3 + T cell proliferation [11], antibacterial activities [12], the inhibition of colon cancer and melanoma cells [13], aromatase inhibitory activity [17], and induction neurite outgrowth in rat PC-12 cells [21].…”

“…As versiol was originally discovered from the fungus Aspergillus versicolor in 1975 [8], a total of 63 congeners have been discovered from several fungal genera [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Some of them showed interesting bioactivities, such as induced CD3 + T cell proliferation [11], antibacterial activities [12], the inhibition of colon cancer and melanoma cells [13], aromatase inhibitory activity [17], and induction neurite outgrowth in rat PC-12 cells [21]. As part of our continuing efforts to discover new and/or bioactivity secondary metabolites from the deep-sea-derived fungi [23][24][25][26][27][28], the fungus Penicillium chrysogenum MCCC 3A00292, isolated from South Atlantic Ocean at the depth of 2076 meters, was chosen for a systematic chemical investigation due to its rich metabolite profile in preliminary thin-layer chromatography (TLC) and high performance liquid chromatography (HPLC) screening.…”