Document Detail


Design, synthesis, and cholesterol-lowering efficacy for prodrugs of berberrubine.
MedLine Citation:
PMID:  20673726     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
In order to enhance oral bioavailability of berberine (BBR) for its cholesterol-lowering efficacy in vivo, a series of ester or ether prodrugs of berberrubine (M1), which is an active metabolite of BBR after first-pass metabolism, were designed, semi-synthesized, and evaluated. Among these M1 prodrugs, compound 5g possessing palmitate at the 9-position showed a moderate LogP value and esterase hydrolysis rate for releasing M1 in blood. Its cholesterol-lowering efficacy in vivo was evaluated in hyperlipidemic SD rats. Compound 5g (100mg/kg/d) reduced blood CHO and LDL-c by 35.8% and 45.5%, respectively, similar to that by BBR. It also exhibited a good safety in rats with no side-effect on liver and kidney function. Therefore, the design of M1 prodrug appears to be an effective strategy to improve pharmacokinetic feature of BBR for its lipid-lowering efficacy in vivo.
Authors:
Ying-Hong Li; Yi Li; Peng Yang; Wei-Jia Kong; Xue-Fu You; Gang Ren; Hong-Bin Deng; Yue-Ming Wang; Yan-Xiang Wang; Jian-Dong Jiang; Dan-Qing Song
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-30
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  18     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  6422-8     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
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