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

Publication date: April 2018 Source:Phytochemistry Letters, Volume 24 Author(s): Magie M. Kapojos, Delfly B. Abdjul, Hiroyuki Yamazaki, Ryota Kirikoshi, Ohgi Takahashi, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, Kazuyo Ukai, Michio Namikoshi 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 μM, respectively, while compounds 4 and 5 were not active at 38–40 μM. 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. Graphical abstract

Source: Phytochemistry Letters - January 23, 2018 Category: Chemistry Source Type: research