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
Research output: Contribution to journal › Journal article › Research › peer-review
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
Original language | English |
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Journal | Journal of Natural Products |
Volume | 83 |
Pages (from-to) | 1598-1610 |
ISSN | 0163-3864 |
DOIs | |
Publication status | Published - 7 Apr 2020 |
ID: 238498506