Anti-inflammatory Mono- and Dimeric Sorbicillinoids from the Marine-Derived Fungus Trichoderma reesei 4670

Abstract

Eight new dimeric sorbicillinoids (1–3, 5–9) and 12 new monomeric sorbicillinoids (10–20, 25), along with five known analogues (4 and 21–24), were isolated from the marine-derived fungus Trichoderma reesei 4670. Their structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, HR-ESIMS, and ECD) and X-ray crystallography. Compound 1, containing a pyrrolidin-2-one moiety, is reported for the first time in the sorbicillinoid family. Compounds 8 and 9 are the first examples of bisorbicillinoids possessing a benzofuro­[2,3-h]­chromene scaffold from a natural source. Compounds 3–11, 13–16, 18, 21, 22, 24, and 25 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide with IC50 values in the range from 0.94 to 38 μM. Structure–activity relationships of the sorbicillinoids were discussed.

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.…”

“…There has been a tremendous increase in pharmacological research on anti-inflammatory of marine-derived molecules, and more than 150 anti-inflammatory compounds derived from marine fungi have been reported past two decades [ 37 , 38 ]. The anti-inflammatory compounds are classified into different chemical classes, such as terpenes [ 39 , 40 ], steroids [ 41 ], polyketides [ 15 ], alkaloids [ 42 ], and peptides [ 43 ]. For example, tanzawaic acid Q (isolated from a marine-derived fungus, Penicillium steckii 108YD142) inhibited the lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and mRNA expressions in RAW 264.7 macrophages.…”

“…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.…”

“…ZH-15 [13]. (13), 3'-hydroxyalternariol 5-O-methyl ether (14), alternariol-1'-hydroxy-9-methyl ether (15), dehydroaltenusin (16), alteryulactone (17), tenuissimasatin (18), 5'-methoxy-6-methyl-biphenyl-3,4,3'-triol (19), altenusin (20), 2,5-dimethyl-7-hydroxychromone (21) and walterolactone C (22) ( Figure 1). Their structures were identified by extensive spectroscopic analyses (1D and 2D NMR, HR-ESIMS, and ECD) and X-ray crystallography, as well as the modified Mosher's method.…”

“…Recently, we searched for anti-inflammatory secondary metabolites from the South China Sea [ 14 , 15 , 16 , 17 ]. EtOAc extract of marine-derived fungus Alternaria sp.…”