1. 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.
- Author
-
Pedersen HA, Ndi C, Semple SJ, Buirchell B, Møller BL, and Staerk D
- Subjects
- Chromatography, High Pressure Liquid, Fatty Acids, Glycoside Hydrolase Inhibitors chemistry, Hypoglycemic Agents metabolism, Magnetic Resonance Spectroscopy, Molecular Structure, Plant Extracts chemistry, Protein Tyrosine Phosphatase, Non-Receptor Type 1 metabolism, Solid Phase Extraction, alpha-Glucosidases metabolism, Hypoglycemic Agents chemistry, Protein Tyrosine Phosphatase, Non-Receptor Type 1 chemistry, Scrophulariaceae chemistry
- Abstract
Ten new branched-chain fatty acid (BCFA) dimers with a substituted cyclohexene structure, five new monomers, and two known monomers, (2 E ,4 Z ,6 E )-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 semipreparative-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 semipreparative-scale HPLC. The dimers were generally more potent than the monomers with IC
50 values ranging from 2 to 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.- Published
- 2020
- Full Text
- View/download PDF