Pancreatic Lipase Inhibitory Cyclohexapeptides from the Marine Sponge-Derived Fungus Aspergillus sp. 151304

Three new cyclohexapeptides, petrosamides A-C (1-3), were isolated from the sponge-derived fungus Aspergillus sp. 151304. Their structures were elucidated by detailed 1D and 2D spectroscopic analyses, and the absolute configurations of the amino acid residues were determined by the advanced Marfey's method. These peptides displayed significant and dose-dependent pancreatic lipase (PL) inhibitory activities, with IC50 values of 7.6 +/- 1.5, 1.8 +/- 0.3, and 0.5 +/- 0.1 mu M, respectively. Further inhibition kinetics analyses showed that compound 3 inhibited PL in a noncompetitive manner, while molecular dynamics simulation revealed that it could bind to PL at the entrance of the catalytic pocket.