PTP1B-inhibiting branched-chain fatty acid dimers from Eremophila oppositifolia subsp. angustifolia identified by high-resolution PTP1B inhibition profiling and HPLC-PDA-HRMS-SPE-NMR analysis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Ten new branched-chain fatty acid (BCFA) dimers with a substituted cyclohexene structure, five new monomers, and two known monomers, (2E,4Z,6E)-5-(acetoxymethyl)tetradeca-2,4,6-trienoic acid and its 5-hydroxymethyl analogue, were identified in the leaf extract of Eremophila oppositifolia subsp. angustifolia using a combination of HPLC-PDA-HRMS-SPE-NMR analysis and semi-preparative-scale HPLC. The dimers could be classified as three types of Diels-Alder reaction products formed between monomers at two different sites of unsaturation of the dienophile. Two of the monomers represent potential biosynthetic intermediates of branched-chain fatty acids. Several compounds were found by high-resolution bioactivity profiling to inhibit PTP1B and were purified subsequently by semi-preparative-scale HPLC. The dimers were generally more potent than the monomers with IC50 values ranging from 2-66 μM, compared to 38-484 μM for the monomers. The ten fatty acid dimers represent both a novel class of compounds and a novel class of PTP1B inhibitors
TidsskriftJournal of Natural Products
Sider (fra-til)1598-1610
StatusUdgivet - 7 apr. 2020

ID: 238498506