6-OH-Phenanthroquinolizidine Alkaloid and Its Derivatives Exert Potent Anticancer Activity by Delaying S Phase Progression
文献类型：期刊论文
| 作者 | Liu, Yuxiu1; Qing, Lihua2; Meng, Chuisong1; Shi, Jiajie2; Yang, Yan2; Wang, Ziwen1; Han, Guifang1; Wang, Yi2; Ding, Jian2 ; Meng, Ling-hua2
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2017-04-13 |
| 卷号 | 60期号:7页码:2764-2779 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.6b01502 |
| 文献子类 | Article |
| 英文摘要 | To discover new phenanthroindolizidine and phenanthroquinolizidine alkaloids as potential anticancer drug candidates, non-natural 6-O-desmethylcryptopleurine (2) and its derivatives were prepared. Most of the new compounds exhibited potent antiproliferative activity against A549 and BEL-7402 cells, with the lowest IC50 being 3 nM. Optically pure 2-R was further evaluated against a panel of 30 cancer cell lines and found to inhibit the proliferation of all tested cell lines, including three multidrug-resistant cell lines, with an average IC50 value of 2.1 nM, which is much lower than that of previously reported phenanthroindolizidine DCB-3503 (1, IC50: 166.7 nM). A mechanistic evaluation showed that 2-R potently inhibited cell growth and colony formation, which are associated with a delay in S phase progression through the inhibition of DNA synthesis. These results along with further study on the safety profile of these compounds will facilitate the discovery of new phenanthroindolizidine and phenanthroquinolizidine alkaloids for use as anticancer drug candidates. |
| WOS关键词 | PHENANTHROINDOLIZIDINE ALKALOIDS ; PHENANTHROQUINOLIZIDINE ALKALOIDS ; CELL-GROWTH ; CYNANCHUM-VINCETOXICUM ; CYTOTOXIC ACTIVITY ; PROTEIN-SYNTHESIS ; ANTITUMOR AGENTS ; CANCER-CELLS ; INHIBITION ; TYLOPHORINE |
| 资助项目 | National Natural Science Foundation of China[21421062] ; National Natural Science Foundation of China[21372131] ; National Natural Science Foundation of China[21672117] ; National Natural Science Foundation of China[81321092] ; Specialized Research Fund for the Doctoral Program of Higher Education[20130031110017] ; Tianjin Natural Science Foundation[16JCZDJC32400] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000399436100011 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272702]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Meng, Ling-hua; Wang, Qingmin |
| 作者单位 | 1.Nankai Univ, Res Inst Elementoorgan Chem, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Yuxiu,Qing, Lihua,Meng, Chuisong,et al. 6-OH-Phenanthroquinolizidine Alkaloid and Its Derivatives Exert Potent Anticancer Activity by Delaying S Phase Progression[J]. JOURNAL OF MEDICINAL CHEMISTRY,2017,60(7):2764-2779. |
| APA | Liu, Yuxiu.,Qing, Lihua.,Meng, Chuisong.,Shi, Jiajie.,Yang, Yan.,...&Wang, Qingmin.(2017).6-OH-Phenanthroquinolizidine Alkaloid and Its Derivatives Exert Potent Anticancer Activity by Delaying S Phase Progression.JOURNAL OF MEDICINAL CHEMISTRY,60(7),2764-2779. |
| MLA | Liu, Yuxiu,et al."6-OH-Phenanthroquinolizidine Alkaloid and Its Derivatives Exert Potent Anticancer Activity by Delaying S Phase Progression".JOURNAL OF MEDICINAL CHEMISTRY 60.7(2017):2764-2779. |
入库方式： OAI收割
来源：上海药物研究所
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