Evaluation of the cytotoxic activity of new jadomycin derivatives reveals the potential to improve its selectivity against tumor cells
文献类型：期刊论文
| 作者 | Fan, Keqiang1; Zhang, Xia1; Liu, Hongchun2 ; Han, Hui1; Luo, Yuanming1; Wang, Qian1; Geng, Meiyu2; Yang, Keqian1
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| 刊名 | JOURNAL OF ANTIBIOTICS
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| 出版日期 | 2012-09 |
| 卷号 | 65期号:9页码:449-452 |
| 关键词 | anti-tumor jadomycin polyketides precursor-directed biosynthesis |
| ISSN号 | 0021-8820 |
| DOI | 10.1038/ja.2012.48 |
| 文献子类 | Article |
| 英文摘要 | The jadomycins are a unique family of angucycline-derived antibiotics with interesting cytotoxic activities. In this work, six new jadomycin derivatives were produced in vivo by providing non-natural amino acids in fermentation media. They were further purified and identified by MS and NMR analyses. The cytotoxicities of these derivatives were evaluated against tumor cell lines MCF-7 and HCT116, as well as the normal human microvascular epithelial cells. The derivatives with alkyl side chains showed similar levels of cytotoxicity as jadomycin B and other known derivatives with nonpolar side chains, with IC50 ranging from 1.3 to 10 mu M; but the activities are not selective as these compounds also showed similar levels of cytotoxicity toward the normal human microvascular epithelial cells in the same concentration range. For the first time, derivatives with amino side chains (jadomycin Orn and K) were prepared and evaluated. Significantly, jadomycin Orn showed differential activity against normal and tumor cell lines. This result points to a new direction to modify jadomycin structure. The insights on the structure-activity relationship of jadomycins will guide further efforts to generate new and improved jadomycin derivatives against tumor cells. The Journal of Antibiotics (2012) 65, 449-452; doi:10.1038/ja.2012.48; published online 20 June 2012 |
| WOS关键词 | STREPTOMYCES-VENEZUELAE ISP5230 ; ANTIBIOTIC BIOSYNTHESIS ; AROMATIC POLYKETIDES ; AMINO-ACIDS ; HEAT-SHOCK ; JADH |
| 资助项目 | National Natural Science Foundation of China[31130001] ; National Natural Science Foundation of China[30670017] ; National Natural Science Foundation of China for Distinguished Young Scholars[30725046] |
| WOS研究方向 | Biotechnology & Applied Microbiology ; Immunology ; Microbiology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000309519600002 |
| 出版者 | JAPAN ANTIBIOTICS RESEARCH ASSOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277954]  |
| 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 | Yang, Keqian |
| 作者单位 | 1.Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Resources, Beijing 100101, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fan, Keqiang,Zhang, Xia,Liu, Hongchun,et al. Evaluation of the cytotoxic activity of new jadomycin derivatives reveals the potential to improve its selectivity against tumor cells[J]. JOURNAL OF ANTIBIOTICS,2012,65(9):449-452. |
| APA | Fan, Keqiang.,Zhang, Xia.,Liu, Hongchun.,Han, Hui.,Luo, Yuanming.,...&Yang, Keqian.(2012).Evaluation of the cytotoxic activity of new jadomycin derivatives reveals the potential to improve its selectivity against tumor cells.JOURNAL OF ANTIBIOTICS,65(9),449-452. |
| MLA | Fan, Keqiang,et al."Evaluation of the cytotoxic activity of new jadomycin derivatives reveals the potential to improve its selectivity against tumor cells".JOURNAL OF ANTIBIOTICS 65.9(2012):449-452. |
入库方式： OAI收割
来源：上海药物研究所
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