Microbial transformation of glycyrrhetinic acid derivatives by Bacillus subtilis ATCC 6633 and Bacillus megaterium CGMCC 1.1741.
Glycyrrhetinic acid (GA), the major bioactive pentacyclic triterpene aglycone of licorice root, was known to play a vital role in anti-ulcer, anti-depressant, anti-inflammatory, and anti-allergic. In this study, we semi-synthesized five GA derivatives by a series of chemical reactions. They were selected as substrates for the biotransformation and yielded thirteen metabolites by Bacillus subtilis ATCC 6633 and Bacillus megaterium CGMCC 1.1741. Their structures were identified on the basis of extensive spectroscopic methods and nine of them were found for the first time. Two main types of reactions, regio- and stereo-selective hydroxylation and glycosylation, especially in the unactivated C-H bonds including C-11, C-19 and C-27, were observed in the biotransformation process, which greatly expand the chemical diversities of GA derivatives. All compounds were tested for their inhibitory effects on nitric oxide (NO) generation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Among them, olean-12-ene-3β,7β,15α,19α,30-pentol (16) and olean-12-ene-3β,7β,15α,27,30-pentol (17) showed significant inhibitory effect with IC50 values of 0.64 and 0.07 μM, respectively.
['Shen|Pingping|P|', 'Zhang|Jian|J|', 'Zhu|Yuyuan|Y|', 'Wang|Wei|W|', 'Yu|Boyang|B|', 'Wang|Weiwei|W|']
D000818:Animals D000893:Anti-Inflammatory Agents D001410:Bacillus megaterium D001412:Bacillus subtilis D001711:Biotransformation D004305:Dose-Response Relationship, Drug D006034:Glycyrrhetinic Acid D008070:Lipopolysaccharides D051379:Mice D008968:Molecular Conformation D009569:Nitric Oxide D000067996:RAW 264.7 Cells D013237:Stereoisomerism D013329:Structure-Activity Relationship
Glycyrrhetinic acid derivatives Pentacyclic triterpene Biotransformation Hydroxylation Glycosylation