Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents

doi:10.1016/j.bmc.2008.10.044

科研成果详情

题名	Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents
作者	Liang, Guang1,2; Shao, Lili 2; Wang, Yi 2; Zhao, Chengguang2; Chu, Yanhui 3; Xiao, Jian2; Zhao, Yu 2; Li, Xiaokun1,2; Yang, Shulin 1
发表日期	2009-03-15
发表期刊	BIOORGANIC & MEDICINAL CHEMISTRY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Curcumin analogues Stability Pharmacokinetics Cytotoxic activity Structure-activity relation
其他关键词	PROSTATE CANCER AGENTS ; BIOLOGICAL EVALUATION ; TELOMERASE ACTIVITY ; ANTITUMOR AGENTS ; ANTICANCER ; INHIBITION ; REDUCTION ; APOPTOSIS ; DESIGN ; ENONES
摘要	Curcumin has a surprisingly wide range of chemo-preventive and chemo-therapeutic activities and is under investigation for the treatment of various human cancers. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Although a number of synthetic modi. cations of curcumin have been studied intensively in order to develop a molecule with enhanced bioactivities, few synthetic studies were done for the improvement of pharmacokinetic profiles. In the present study, a series of mono-carbonyl analogues of curcumin were designed and synthesized by deleting the reactive beta-diketone moiety, which was considered to be responsible for the pharmacokinetic limitation of curcumin. The results of the in vitro stability studies and in vivo pharmacokinetic studies indicated that the stability of these mono-carbonyl analogues was greatly enhanced in vitro and their pharmacokinetic profiles were also significantly improved in vivo. Furthermore, the cytotoxic activities of mono-carbonyl analogues were evaluated in seven different tumor cell lines by MTT assay and the structure-activity relation (SAR) was discussed and concluded. The results suggest that the five-carbon linker-containing analogues of curcumin may be favorable for the curcumin-based drug development both pharmacokinetically and pharmacologically. (C) 2009 Published by Elsevier Ltd.
资助项目	National Natural Science Funding of ChinaNational Natural Science Foundation of China (NSFC) [20802054]; General Grant of Zhejiang Administration of Chinese Traditional Medicine [2007CA08079]; NJUST Innovative Ph. D. Training Project; Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents
出版者	PERGAMON-ELSEVIER SCIENCE LTD
出版地	OXFORD
ISSN	0968-0896
EISSN	1464-3391
卷号	17 期号:6 页码:2623-2631
DOI	10.1016/j.bmc.2008.10.044
页数	9
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
WOS记录号	WOS:000264236700057
收录类别	SCIE ; SCOPUS
URL	查看原文
PubMed ID	19243951
SCOPUSEID	2-s2.0-62149086696
通讯作者地址	[Li, Xiaokun]College of Chemical Engineering,Nanjing University of Science and Technology,200 Xiaolingwei St,China
Scopus学科分类	Biochemistry;Molecular Medicine;Molecular Biology;Pharmaceutical Science;Drug Discovery;Clinical Biochemistry;Organic Chemistry
引用统计	被引频次：282[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/6966
专题	药学院（分析测试中心）研究生工作部（研究生院）
通讯作者	Li, Xiaokun
作者单位	1.College of Chemical Engineering,Nanjing University of Science and Technology,200 Xiaolingwei St,China; 2.School of Pharmacy,Wenzhou Medical College,1210 College Town,China; 3.Heilongjiang Province Key Laboratory of Anti-fibrosis Biotherapy,Mudanjiang Medical College,China
第一作者单位	温州医科大学
推荐引用方式 GB/T 7714	Liang, Guang,Shao, Lili,Wang, Yi,et al. Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2009,17(6):2623-2631.
APA	Liang, Guang., Shao, Lili., Wang, Yi., Zhao, Chengguang., Chu, Yanhui., ... & Yang, Shulin. (2009). Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents. BIOORGANIC & MEDICINAL CHEMISTRY, 17(6), 2623-2631.
MLA	Liang, Guang,et al."Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents".BIOORGANIC & MEDICINAL CHEMISTRY 17.6(2009):2623-2631.