Isolation, structure elucidation and PTP1B inhibitory activity of serrulatane diterpenoids from the roots of Myoporum insulare. (October 2020)

• Record Type: Journal Article
• Authors: Kjaerulff, Louise; Jensen, Alexander Baekager Just; Ndi, Chi; Semple, Susan; Møller, Birger Lindberg; Staerk, Dan
• Is Part Of: Phytochemistry letters. Volume 39(2020)
• Page Start: 49
• Page End: 56
• Publication Date: 2020-10
• Subjects: Myoporum insulare -- Scrophulariaceae -- Eremophila -- Serrulatane -- Type 2 diabetes -- PTP1B; Botanical chemistry -- Periodicals; Chimie végétale -- Périodiques; 572.205
• DOI: 10.1016/j.phytol.2020.07.001
• Languages: English
• ISSNs: 1874-3900

Abstract

Graphical abstract: Highlights: First phytochemical investigation of the roots of Myoporum insulare . Four new and five known diterpenoids were isolated by analytical-scale HPLC. Dual high-resolution α-glucosidase/PTP1B inhibition profiling revealed bioactivity. The diterpene alkaloid microthecaline A found outside Eremophila for the first time. Abstract: A methylene chloride extract of Myoporum insulare R. Br. (Scrophulariaceae) root material was investigated by dual high-resolution PTP1B/α-glucosidase inhibition profiling and LC-PDA-HRMS. Subsequent analytical-scale separation of the crude extract afforded serrulatanes 1 -9 of which 2 ((1 R, 11 S, 18 R )-5, 18-epoxyserrulat-3, 14-dien-8, 18-diol or myoporulatane A), 6 ((1 R, 4 S, 11 S )-8-hydroxy-serrulat-14-en-18, 5-olide or myoporulatane B), 7 ((1 R, 4 S, 11 S )-serrulat-14-en-5, 8, 18-trione or myoporulatane C), and 9 ((1 S, 2 R, 4 S, 11 S )-2β-hydroxy-serrulat-14-ene or myoporulatane D) are previously unreported. The structures of all isolated compounds were established by HRMS as well as 1D and 2D NMR analysis. Relative configurations were determined from combined analyses of chemical shifts, J -coupling constants and ROESY correlations, and absolute configurations were tentatively assigned by comparison to previous studies and from biosynthetic arguments. Compounds correlated with PTP1B inhibitory activity in the high-resolution inhibition profile were tested after isolation. However, the pure compounds exhibited weak or essentially no inhibitory activity against PTP1B with IC50 values of 97.4 μM for 2, 3.0 mM for 4, and > 100 μM for 7 . This is the first study of the root chemistry of M. insulare .