Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues
Wang, Yue-Hu1,2; Goto, Masuo1; Wang, Li-Ting1; Hsieh, Kan-Yen1; Morris-Natschke, Susan L.1; Tang, Gui-Hua3; Long, Chun-Lin2,4; Lee, Kuo-Hsiung1,5; Wang,YH (reprint author),Univ N Carolina,Eshelman Sch Pharm,Nat Prod Res Labs,Chapel Hill,NC 27599 USA.; wangyuehu@mail.kib.ac.cn; khlee@unc.edu
2014-10-15
发表期刊BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN0960-894X
卷号24期号:20页码:4818-4821
产权排序第二
摘要Twenty-five amide alkaloids (1-25) from Piper boehmeriifolium and 10 synthetic amide alkaloid derivatives (39-48) were evaluated for antiproliferative activity against eight human tumor cell lines, including chemosensitive and multidrug-resistant (MDR) cell lines. The results suggested tumor type-selectivity. 1-[7-(3,4,5-Trimethoxyphenyl) heptanoyl] piperidine (46) exhibited the best inhibitory activity (IC50 = 4.94 mu M) against the P-glycoprotein (P-gp)-overexpressing KBvin MDR sub-line, while it and all other tested compounds, except 9, were inactive (IC50 > 40 mu M) against MDA-MB-231 and SK-BR-3. Structure-activity relationships (SARs) indicated that (i) 3,4,5-trimethoxy phenyl substitution is critical for selectivity against KBvin, (ii) the 4-methoxy group in this pattern is crucial for antiproliferative activity, (iii) double bonds in the side chain are not needed for activity, and (iv), in arylalkenylacyl amide alkaloids, replacement of an isobutylamino group with pyrrolidin-1-yl or piperidin-1-yl significantly improved activity. Further study on Piper amides is warranted, particularly whether side chain length affects the ability to overcome the MDR cancer phenotype. (C) 2014 Elsevier Ltd. All rights reserved.
关键词Piper Piperaceae Amide Alkaloids Cytotoxicity Multidrug Resistance
资助信息Natural Science Foundation of Yunnan Province, China [2011FZ205]; NIH from the National Cancer Institute [CA177584]
学科领域Pharmacology & Pharmacy ; Chemistry
DOI10.1016/j.bmcl.2014.08.063
收录类别SCI ; IC
语种英语
WOS研究方向Pharmacology & Pharmacy ; Chemistry
WOS类目Chemistry, Medicinal ; Chemistry, Organic
WOS记录号WOS:000342575200009
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文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/18408
专题资源植物与生物技术所级重点实验室
通讯作者Wang,YH (reprint author),Univ N Carolina,Eshelman Sch Pharm,Nat Prod Res Labs,Chapel Hill,NC 27599 USA.; wangyuehu@mail.kib.ac.cn; khlee@unc.edu
作者单位1.Univ N Carolina, Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA
2.Chinese Acad Sci, Kunming Inst Bot, Key Lab Econ Plants & Biotechnol, Kunming 650201, Peoples R China
3.Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
4.Minzu Univ China, Coll Life & Environm Sci, Beijing 100081, Peoples R China
5.China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung 40447, Taiwan
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Wang, Yue-Hu,Goto, Masuo,Wang, Li-Ting,et al. Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2014,24(20):4818-4821.
APA Wang, Yue-Hu.,Goto, Masuo.,Wang, Li-Ting.,Hsieh, Kan-Yen.,Morris-Natschke, Susan L..,...&khlee@unc.edu.(2014).Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,24(20),4818-4821.
MLA Wang, Yue-Hu,et al."Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 24.20(2014):4818-4821.
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