Protein tyrosine phosphatase 1B inhibitory polybromobiphenyl ethers and monocyclofarnesol-type sesquiterpenes from the Indonesian marine sponge Lamellodysidea cf. herbacea

Three known polybromobiphenyl ether derivatives, 2-(2',4'-dibromophenoxy)-3,5-dibromophenol (1), 2-(2',4'dibromophenoxy)-4,6-dibromophenol (2), and 2-(2'-dibromophenoxy)-3,4,5,6-tetrabromophenol (3), were identified as PTP1B inhibitors from the Indonesian marine sponge Lamellodysidea sp. (cf. L. herbacea) together with two new monocyclofarnesol-derived sesquiterpenes, lamellolactones A (4) and B (5). The structures of 4 and 5 were elucidated based on their spectroscopic data and comparisons with those for related compounds. Compounds 1-3 inhibited PTP1B activity with IC50 values of 5.3, 7.8, and 5.3 mu M, respectively, while compounds 4 and 5 were not active at 38-40 mu M. The selective activities of 1-3 against PTP1B over the other PTPs (T-cell PTP, CD45 tyrosine phosphatase, and vaccinia H-1-related phosphatase) showed that the position and/or number of Br atoms affected their inhibitory activities.