| Summary: | The biotransformation of vulgarin <b>(1)</b>, an eudesmanolides-type sesquiterpene lactone obtained from <i>Artemisia judaica</i>, by the microorganism, <i>Aspergillus niger</i>, was carried out to give three more polar metabolites; 1-<i>epi</i>-tetrahydrovulgarin (1α,4α-dihydroxy-5αH,6,11βH-eudesman-6,12-olide <b>(2)</b>, 20% yield, 1α,4α-dihydroxyeudesm-2-en-5αH,6,11βH-6,12-olide <b>(3a)</b>, 10% yield, and C-1 epimeric mixture <b>(3a, b)</b>, 4% yield, in a ratio of 4:1, <b>3a/3b</b>. The structures of vulgarin and its metabolites were elucidated by 1 and 2D NMR spectroscopy in conjunction with HRESIMS. Metabolites <b>(3a)</b> and <b>(3b)</b> are epimers, and they are reported here for the first time as new metabolites obtained by biotransformation by selective reduction at C-1. Vulgarin and its metabolites were evaluated as anti-inflammatory agents using the human cyclooxygenase (COX) inhibitory assay. The obtained data showed that <b>(1)</b> exhibited a good preferential inhibitory activity towards COX-2 (IC50 = 07.21 ± 0.10) and had a moderate effect on COX-1 (IC50 = 11.32 ± 0.24). Meanwhile, its metabolite <b>(3a)</b> retained a selective inhibitory activity against COX-1 (IC50 = 15.70 ± 0.51). In conclusion, the results of this study revealed the necessity of the presence α, β unsaturated carbonyl group in <b>(1)</b> for better COX-2 inhibitory activity. On the other hand, the selectivity of <b>(1)</b> as COX-1 inhibitor may be enhanced via the reduction of C-1 carbonyl group.
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