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
| Autor: | Chi P. Ndi, Bevan Buirchell, Susan J. Semple, Dan Staerk, Birger Lindberg Møller, Hans Pedersen |
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| Přispěvatelé: | Hans, Albert Pedersen, Ndi, Chi, Semple, Susan J, Buirchell, Bevan, Moller, Birger Lindberg, Staerk, Dan |
| Rok vydání: | 2020 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Degree of unsaturation 010405 organic chemistry Stereochemistry Organic Chemistry Cyclohexene Pharmaceutical Science Fatty acid Nuclear magnetic resonance spectroscopy 01 natural sciences High-performance liquid chromatography 0104 chemical sciences Analytical Chemistry 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Monomer Complementary and alternative medicine chemistry Drug Discovery Molecular Medicine Molecule Solid phase extraction |
| Zdroj: | Journal of Natural Products. 83:1598-1610 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | 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 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 IC50 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. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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