A New Hypoglycemic Prenylated Indole Alkaloid N-Oxide from Endophytic Fungus Pallidocercospora crystalline.

A new prenylated indole alkaloid-Penicimutamide C N-oxide (1), a new alkaloid penicimutamine A (2), along with six known alkaloids were isolated from an endophytic fungus Pallidocercospora crystallina. A simple and accurate method was used to determine the N-O bond in the N-oxide group of 1. By using a ß-cell ablation diabetic zebrafish model, compounds 1, 3, 5, 6 and 8 showed significantly hypoglycemic activities under the concentration of 10 µM. Further studies revealed that compounds 1 and 8 lowered the glucose level through promoting glucose uptake in zebrafish. In addition, all eight compounds showed no acute toxicity, teratogenicity, nor vascular toxicity in zebrafish under the concentrations range from 2.5 µΜ to 40 µM. Importantly, these results provide new lead compounds for the development of antidiabetes strategies.

Brasilterpenes A-E, Bergamotane Sesquiterpenoid Derivatives with Hypoglycemic Activity from the Deep Sea-Derived Fungus Paraconiothyrium brasiliense HDN15-135.

Five bergamotane sesquiterpenoid derivatives, brasilterpenes A-E (1-5), bearing an unreported spiral 6/4/5 tricyclic ring system, were isolated from the deep sea-derived ascomycete fungus Paraconiothyrium brasiliense HDN15-135. Their structures, including absolute configurations, were established by extensive spectroscopic methods complemented by single-crystal X-ray diffraction analyses, electronic circular dichroism (ECD), and density-functional theory (DFT) calculations of nuclear magnetic resonance (NMR) data including DP4+ analysis. The hypoglycemic activity of these compounds was assessed using a diabetic zebrafish model. Brasilterpenes A (1) and C (3) significantly reduced free blood glucose in hyperglycemic zebrafish in vivo by improving insulin sensitivity and suppressing gluconeogenesis. Moreover, the hypoglycemic activity of compound 3 was comparable to the positive control, anti-diabetes drug rosiglitazone. These results suggested brasilterpene C (3) had promising anti-diabetes potential.

Penipyrols C-G and methyl-penipyrol A, α-pyrone polyketides from the mangrove derived fungus Penicillium sp. HDN-11-131.

Six new α-pyrone polyketides, penipyrols C-G (1-5) and methyl-penipyrol A (6), together with one biogenetically related known compound, penipyrol A (7), were isolated from the extract of fungus Penicillium sp. HDN-11-131. Their structures including the absolute configurations were established by extensive spectroscopic analysis, Mosher's method, and ECD calculations as well as biogenic considerations. Compounds 1-4 possess a rare skeleton featuring γ-butyrolactone linked to α-pyrone ring through double bond. Compound 1 can induce pancreatic ß-cell regeneration in zebrafish at 10 µM, which demonstrated promising anti-diabetes potential.