Novel anthraquinone derivatives as inhibitors of protein tyrosine phosphatases and indoleamine 2,3-dioxygenase 1 from the deep-sea derived fungusAlternaria tenuissimaDFFSCS013

Abstract

A novel hydroanthraquinone possessing an unprecedented hexacyclic spiro-fused ring system, anthrininone A (1), and two new anthraquinones, anthrininones B and C (2 and 3), were obtained from the deep-sea derived fungus Alternaria tenuissima.

Secondary Metabolites with Nitric Oxide Inhibition from Marine-Derived Fungus Alternaria sp. 5102

“…For isocoumarins with 6/6/5 system (8 and 9), the keto carbonyl group at C-9 made no difference to the anti-inflammatory activity, while the hydroxyl group at C-9 made a more positive contribution to the anti-inflammatory activity. For another isocoumarins with 6/6/6 system (11)(12)(13)(14)(15), the substitution with the hydroxyl group at C-10 made a more positive contribution to the anti-inflammatory activity, while other substitution made no difference to the anti-inflammatory activity.…”

“…Therefore, the structure of 3 was established as (4S,5S,6S,10R)-3 and named alternaterpenoid A. 12 27.5, CH2 Figure S29), compound 4 was found to have a molecular formula (C15H22O2) as that of 3. The 1D NMR data ( Figure S30 and S31) of 4 were closely comparable to those of 3, except for the change in the substitution group on C-11(71.3)/C-14(27.0), resulting in one hydroxymethyl on C-7(164.6) and C-4 (51.0) with methyl in 4.…”

“…The theoretical ECD spectra were calculated by a quantum chemical method at the [RB3LYP/6311+G(2d,p)] level, and the predicted ECD curve of (5S,6R,10R)-4 was in good agreement with that of the experimental one ( Figure 6). Therefore, the structure of 4 was established as (5S,6R,10R)-4, and named alternaterpenoid B. Additionally, 18 known compounds were identified as isobenzofuranone A (5) [23], isoochracinic acid (6) [24], (R)-1,6-dihydroxy-8-methoxy-3a-methyl-3,3a-dihydrocyclopenta[c]isochromene-2,5-dione (7) [25], dihydroaltenuenes A (8) [25], phialophriol (9) [25,26], ± talaroflavone (10), alternariol-9-O-methyl ether (11) [27], alternariol (12) In this work, all isolated compounds (1-22) were evaluated for their inhibition of nitric oxide (NO) production in RAW264.7 cells activated by lipopolysaccharide (LPS) using the Griess assay with indomethacin as a positive control (Table 3). Compounds 2, 3, 7, 9,10, 12-15, 17,18 and 20-22 showed stronger anti-inflammatory activity compared to the positive control indomethacin whose IC 50 was 35.8 ± 5.7 µM.…”

“…Chemical investigation of an extract of marine-derived fungus Alternaria sp. 5102 from rice medium led to the discovery of two new benzofurans, alternabenzofurans A and B (1 and 2) and two new sesquiterpenoids, alternaterpenoids A and B (3 and 4), along with 18 known polyketides (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Their structures were clearly elucidated by extensive spectroscopic analyses and X-ray crystallography, as well as the modified Mosher's method.…”

“…These metabolites exhibited a variety of biological activities such as cytotoxic, antimicrobial, enzyme inhibitor properties [10]. For instances, naphtho-γ-pyrones pyrophen displayed anti-fungal activity against C. albicans from the marine-derived fungus Alternaria alternate D2006 [11], anthraquinone anthrininone A showed significant inhibition activity against indoleamine 2,3-dioxygenase 1 (IDO1) from the deep-sea derived fungus Alternaria tenuissima DFFSCS013 [12], drimane meroterpenoid alternarin A revealed effective inhibition of spontaneous synchronous Ca 2+ oscillations from the coral-associated fungi Alternaria sp. ZH-15 [13].…”