Microbial transformation of glycyrrhetinic acid derivatives by Bacillus subtilis ATCC 6633 and Bacillus megaterium CGMCC 1.1741 |
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| Affiliation: | 1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China;2. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China;1. Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Granada, E-18071 Granada, Spain;2. Departamento de Microbiología, Facultad de Ciencias, Universidad de Granada, E-18071 Granada, Spain;1. Department of Microbiology, Institute of Biological Sciences, University Federal of Minas Gerais, Av. Antônio Carlos 6627, P.O. Box 486, 31270-901 Belo Horizonte, MG, Brazil;2. Department of Pharmaceutical Products, Pharmacy School of UFMG, University Federal of Minas Gerais, Belo Horizonte, MG, Brazil;3. Department of Physiology and Biophysics, Institute of Biological Sciences, University Federal of Minas Gerais, Belo Horizonte, MG, Brazil;4. Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School, and Brown University, Providence, RI, USA;1. The Key Laboratory of Leather Chemistry and Engineering of Ministry of Education, Sichuan University, Chengdu, Sichuan 610065, PR China;2. National Engineering Laboratory of Clean Technology for Leather Manufacture, Sichuan University, Chengdu 610065, PR China;1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China;2. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China |
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| Abstract: | 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. |
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| Keywords: | Glycyrrhetinic acid derivatives Pentacyclic triterpene Biotransformation Glycosylation Hydroxylation |
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