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Finding novel anti-diabetic compounds with effective suppression activities against hepatic glucagon response is urgently required for the development of new drugs against diabetes. Fungi are well known for their ability to produce new bioactive secondary metabolites. As part of our ongoing research, five new indole-terpenoids (1–5), named encindolenes D-H, were isolated from the fungus Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne. The structures of the compounds were elucidated by spectroscopic data and ECD analysis. In the anti-diabetic activity assay, compounds 1–5 could inhibit the hepatic glucose production with EC50 values of 17.6, 30.1, 21.3, 9.6, and 9.9 μM, respectively, and decrease the cAMP contents in glucagon-induced HepG2 cells.

Two new benzoic acids, cladoslide A (1) and cladoslide B (2); one new β-carboline derivative, cladospomine (3); and one new pyridin-2(1H)-one, cladoslide C (4), were isolated from the fermentation cultures of the mangrove-derived fungus Cladosporium sp. HNWSW-1, along with the previously reported N-acetyl-β-oxotryptamine (5), (4S,5S,11R)-iso-cladospolide B (6), (4S,5S,11S)-iso-cladospolide B (7), and (4R,5S,11R)-iso-cladospolide B (8). Their structures were elucidated by spectroscopic analysis, Rh2(OCOCF3)4-induced ECD experiments, and Marfey’s method. Compound 1 showed cytotoxicity against the K562 cell line with IC50 values of 13.10 ± 0.08 μM. Moreover, compounds 1 and 5 exhibited inhibitory activity against α-glycosidase with IC50 values of 0.32 ± 0.01 mM and 0.17 ± 0.01 mM, respectively.

Ganoderma fungi have long been used as functional foods and traditional medicines in Asian countries. Ganoderma ahmadii is one of the main species of Ganoderma fungi distributed in Hainan province of China, the fruiting bodies of which have been used in folk to lower blood sugar for a long time. A chemical investigation of the fruiting bodies of Ganoderma ahmadii led to the isolation of seven new meroterpenoids, named ganoduriporols F-L (1–7). The chemical structures of the compounds were elucidated by spectroscopic data including HRESIMS and 2D NMR. Compounds 5–7 represent the first examples of ganoduriporol-type meroterpenoids bearing oxepane rings in their skeletons. Compounds 1–4 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) comparable to the positive control Na3VO4, with IC50 values of 17, 20, 19, and 23 μM, respectively.