Microbial Transformation of the Sesquiterpene Lactone, Vulgarin, by Aspergillus niger

The biotransformation of vulgarin (1), an eudesmanolides-type sesquiterpene lactone obtained from Artemisia judaica, by the microorganism, Aspergillus niger, was carried out to give three more polar metabolites; 1-epi-tetrahydrovulgarin (1 alpha,4 alpha-dihydroxy-5 alpha H,6,11 beta H-eudesman-6,12-olide (2), 20% yield, 1 alpha,4 alpha-dihydroxyeudesm-2-en-5 alpha H,6,11 beta H-6,12-olide (3a), 10% yield, and C-1 epimeric mixture (3a, b), 4% yield, in a ratio of 4:1, 3a/3b. The structures of vulgarin and its metabolites were elucidated by 1 and 2D NMR spectroscopy in conjunction with HRESIMS. Metabolites (3a) and (3b) 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 (1) 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 (3a) 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 alpha, beta unsaturated carbonyl group in (1) for better COX-2 inhibitory activity. On the other hand, the selectivity of (1) as COX-1 inhibitor may be enhanced via the reduction of C-1 carbonyl group.

Automated summary

The biotransformation of vulgarin, a sesquiterpene lactone obtained from Artemisia judaica, was performed by Aspergillus niger to produce three more polar metabolites. The structures of these metabolites were determined using NMR spectroscopy and HRESIMS. The anti-inflammatory activity of vulgarin and its metabolites was evaluated, and vulgarin showed preferential inhibitory activity against COX-2, while its metabolite (3a) exhibited selective inhibition against COX-1.