A bromopyrrole-containing diterpene alkaloid from the Okinawan marine sponge Agelas nakamurai activates the insulin pathway in Huh-7 human hepatoma cells by inhibiting protein tyrosine phosphatase 1B. Issue 10 (15th May 2017)

• Record Type: Journal Article
• Authors: Yamazaki, Hiroyuki; Kanno, Syu-ichi; Abdjul, Delfly B.; Namikoshi, Michio
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 10(2017)
• Page Start: 2207
• Page End: 2209
• Publication Date: 2017-05-15
• Subjects: Agelasine G -- Ageline B -- Marine sponge -- Protein tyrosine phosphatase 1B -- Inhibitor; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.03.033
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Agelasine G (1 ), a known bromine-containing diterpene alkaloid, was isolated as a new type of protein tyrosine phosphatase (PTP) 1B inhibitor together with ageline B (2 ), an inactive debromo-derivative of1, from the marine sponge Agelas nakamurai collected at Iriomote Island in Okinawa, Japan. Further biological evaluations revealed that compound1 exhibited selective inhibitory activity against PTP1B over T-cell PTP and CD45 phosphatase. Compound1 also enhanced the insulin-stimulated phosphorylation levels of Akt in Huh-7 cells more strongly than compound2 . The results obtained in this study suggest that compound1 activates the insulin signaling pathway by inhibiting PTP1B activity.