Identification of a potent xanthine oxidase inhibitor from oxidation of caffeic acid |
| |
| Institution: | 1. Graduate School of Integrated Arts and Sciences, University of Tokushima, Tokushima 770-8502, Japan;2. Faculty of Human Life Science, Shikoku University, Tokushima 771-1192, Japan;1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China;2. Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, China;1. Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Culture Road, Shenhe District, Shenyang 110016, China;2. School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China;3. Department of Pharmacology, Shenyang Pharmaceutical University, 103 Culture Road, Shenhe District, Shenyang 110016, China;1. Laboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, India;2. Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, India;3. Centre for Genetic Diseases and Molecular Medicine, Central University of Punjab, Bathinda 151 001, India;1. College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea;2. Research & Development, LG Life Sciences Ltd, 188 Munji-ro, Yuseong-gu, Daejeon 305-380, Republic of Korea;1. Center for Biomedicinal Science, Faculty of Medicine, University of Nis, Bulevar Dr Zorana Djindjica 81, 18000 Nis, Serbia;2. Institute of Biochemistry, Faculty of Medicine, University of Nis, Bulevar Dr Zorana Djindjica 81, 18000 Nis, Serbia;3. Laboratory of Structural Organic Analysis, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Build. 9, 1113 Sofia, Bulgaria;4. Faculty of Technology, University of Nis, Bulevar oslobodjenja 124, 16000 Leskovac, Serbia;5. Department of Pharmaceutical Chemistry, University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, SI-1000, Slovenia;6. Department of Chemistry, Faculty of Medicine, University of Nis, Bulevar Dr Zorana Djindjica 81, 18000 Nis, Serbia |
| |
| Abstract: | Inhibitory activity of Fe-ion-catalyzed radical oxidation products from 22 types of phenolic compounds toward xanthine oxidase (XO) was investigated. Phenols are readily oxidizable compounds in nature and, thus, showed potent antioxidant activities. Among the phenols screened in this study, noticeable activity was observed in the oxidation product of caffeic acid, whereas almost no XO-inhibitory activity of caffeic acid was observed. Assay-guided purification of the oxidation product of caffeic acid afforded a highly potent XO inhibitor, with an IC50 value that was calculated to be 60 nmol L−1, which indicated XO-inhibitory activity much stronger than that of allopurinol (IC50 = 1 μmol L−1), a potent XO inhibitor and excellent medicine for the treatment of gout. The chemical structure of this new XO inhibitor was investigated by one- and two-dimensional NMR and HR–ESI–MS analyses, and the unique tetracyclic structure was confirmed by synthesis starting from commercially available 1,2,4-trimethoxybenzene and 3,4-dimethoxylbenzoyl chloride. |
| |
| Keywords: | Antioxidant Caffeic acid Polyphenol oxidation Xanthine oxidase inhibitor Structure determination Free radicals |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
