| 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 | |
| Source Publication | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
 |
| ISSN | 0960-894X |
| Volume | 24Issue:20Pages:4818-4821 |
| Abstract | 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. |
| Keyword | Piper Piperaceae Amide Alkaloids Cytotoxicity Multidrug Resistance |
| Subject Area | Pharmacology & Pharmacy ; Chemistry |
| DOI | 10.1016/j.bmcl.2014.08.063 |
| Indexed By | SCI ; IC |
| Language | 英语 |
| WOS ID | WOS:000342575200009 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.kib.ac.cn/handle/151853/18408 |
| Collection | 资源植物与生物技术所级重点实验室 |
| Corresponding Author | 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 |
| Affiliation | 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 |
| Recommended Citation GB/T 7714 | 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. |
| Files in This Item: | ||||||
| File Name/Size | DocType | Version | Access | License | ||
| Wang-2014-Multidrug （492KB） | 开放获取 | CC BY-NC-SA | View Application Full Text | |||
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment