New preaustinoids from a marine-derived fungal strain Penicillium sp. SF-5497 and their inhibitory effects against PTP1B activity

Chemical investigation of the marine-derived fungal isolate Penicillium sp. SF-5497 resulted in the isolation of two new preaustinoid-related meroterpenoids, named preaustinoid A6 (1) and preaustinoid A7 (2), along with three known metabolites (3-5). Their structures were elucidated by extensive spectroscopic analyses, such as 1D and 2D NMR and MS data. Among these, compounds 1 and 3 inhibited PTP1B activity in a dose-dependent manner, with IC50 values of 17.6 and 58.4 mu M, respectively. Furthermore, kinetic analyses indicated that compound 1 inhibited PTP1B in a noncompetitive manner, with the K-i value of 17.0 mu M.