Immunosuppressive Sesquiterpenoids from the Edible Mushroom Craterellus odoratus

Abstract

The aim of this work was to comprehensively understand the chemical constituents of the edible mushroom Craterellus ordoratus and their bioactivity. A chemical investigation on this mushroom led to the isolation of 23 sesquiterpenoids including eighteen previously undescribed bergamotane sesquiterpenes, craterodoratins A–R (1–18), and one new victoxinine derivative, craterodoratin S (19). The new structures were elucidated by detailed interpretation of spectrometric data, theoretical nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculations, and single-crystal X-ray crystallographic analysis. Compounds 1 and 2 possess a ring-rearranged carbon skeleton. Compounds 3, 10, 12–15, 19, 20 and 23 exhibit potent inhibitory activity against the lipopolysaccharide (LPS)-induced proliferation of B lymphocyte cells with the IC50 values ranging from 0.67 to 22.68 μM. Compounds 17 and 20 inhibit the concanavalin A (ConA)-induced proliferation of T lymphocyte cell with IC50 values of 31.50 and 0.98 μM, respectively. It is suggested that C. ordoratus is a good source for bergamotane sesquiterpenoids, and their immunosuppressive activity was reported for the first time. This research is conducive to the further development and utilization of C. ordoratus.

Meroterpenoids with Immunosuppressive Activity from Edible Fungus Craterellus odoratus

“…Finally, the structure of compound 1 was established. It was named craterodoratin T after the name given in our previous work [ 14 ].…”

“…Nutritional and biochemical analysis studies showed that a good amount of proteins, carbohydrates, reducing and non-reducing sugars, phenolics, flavonoids, β-carotene, and lycopene were found in the fresh fruiting bodies of C. odoratus [ 9 ]. Our previous studies on the secondary metabolites of C. odoratus have reported a series of polyketides, meroterpenes, and bergamotane-type sesquiterpenes [ 10 , 11 , 12 , 13 , 14 ]. Of them, craterellin B is a merosesquiterpenoid that showed significant inhibitory activity against the isozyme of human 11β-hydroxysteroid dehydrogenases (11β-HSD1), with an IC 50 value of 3.5 μ g/mL [ 10 ], while craterellin C is also a merosesquiterpenoid from C. odoratus that showed inhibitory activities against two isozymes of human 11β-HSD1 and 11β-HSD2, with IC 50 values of 14.8 and 25.4 μ g/mL, respectively [ 10 ].…”

“…Craterellin C also showed inhibitory activity against the human embryonic kidney 293 cell, with an IC 50 value of 50.9 μ M [ 15 ]. In addition, a few bergamotane sesquiterpenoids from C. odoratus exhibited potent inhibitory activity against the lipopolysaccharide (LPS)-induced proliferation of B lymphocyte cells or against the concanavalin A (ConA)-induced proliferation of T lymphocyte cells [ 14 ]. These data suggest that C. odoratus is a good source of bioactive sesquiterpenes.…”

Two Pairs of New Bisabolane‐Type Sesquiterpenoids from Aspergillus sydowii

“…[21] To fully explore the secondary metabolites of this strain, we studied the isolation and structure characterization of A. sydowii derived from deep-sea sediments. Two pairs of new bisabolanetype sesquiterpenoids, (+)-aspersydowin A (7S) [(+)-1], (À )aspersydowin A (7R) [(À )-1], (+)-aspersydowin B (7S,11S) [(+)-2], (À )-aspersydowin B (7R,11R) [(À )-2], together with six known compounds (3)(4)(5)(6)(7)(8) were obtained. The absolute configurations of compounds 1 and 2 were ascertained by their experimental electronic circular dichroism (ECD) spectra.…”

“…Bisabolane-type sesquiterpenoids have been reported in some fungi, such as Didiscus sp., [1][2][3] Arenochalina sp., [4] Epipolasis sp., [5] and Myrmekioderma sp. [6] Some of bisabolane-type sesquiterpenoids exhibited diverse structural features with a wide range of bioactivities, including immunosuppressive, [7,8] antiatherosclerotic [9] and anti-inflammatory activities. [10] The fungus Aspergillus sydowii is a rich source of structurally diverse natural products with a variety of biological properties, such as cytotoxicity, [11][12][13][14] antitumor, [15][16][17] antibacterial, [18] and anti-inflammatory activities.…”