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
Date
2020
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Hans, A.P.
Ndi, C.
Semple, S.J.
Buirchell, B.
Moller, B.L.
Staerk, D.
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Journal of natural products, 2020; 83(5):1598-1610
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Abstract
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.
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Copyright 2020 American Chemical Society and American Society of Pharmacognosy