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

被引:3
作者
ElGamal, Reem A. [1 ]
Galala, Amal A. [1 ]
Abdel-Kader, Maged S. [2 ,3 ]
Badria, Farid A. [1 ]
Soliman, Amal F. [1 ]
机构
[1] Mansoura Univ, Fac Pharm, Pharmacognosy Dept, Mansoura 35516, Egypt
[2] Prince Sattam Bin Abdulaziz Univ, Coll Pharm, Dept Pharmacognosy, Al Kharj 11942, Saudi Arabia
[3] Alexandria Univ, Fac Pharm, Dept Pharmacognosy, Alexandria 21215, Egypt
来源
MOLECULES | 2023年 / 28卷 / 09期
关键词
vulgarin; biotransformation; Aspergillus niger; vulgarin metabolites; COX inhibitors; SELECTIVE COX-2 INHIBITORS; BIOTRANSFORMATION; CONVERSION; CYCLOOXYGENASE-1;
D O I
10.3390/molecules28093729
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:11
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