Co-Prodrugs of 7-Ethyl-10-hydroxycamptothecin and Vorinostat with in Vitro Hydrolysis and Anticancer Effects
文献类型：期刊论文
| 作者 | Liu, Shuangxi2; Hu, Zonglong1,3; Zhang, Qiumeng1,2; Zhu, Qiwen2; Chen, Yi1 ; Lu, Wei2
|
| 刊名 | ACS OMEGA
 |
| 出版日期 | 2020-01-14 |
| 卷号 | 5期号:1页码:350-357 |
| ISSN号 | 2470-1343 |
| DOI | 10.1021/acsomega.9b02786 |
| 通讯作者 | Zhang, Qiumeng(qiumeng-zhang@foxmail.com) ; Chen, Yi(ychen@simm.ac.cn) ; Lu, Wei(wlu@chem.ecnu.edu.cn) |
| 英文摘要 | 7-Ethyl-10-hydroxycamptothecin (SN38) and vorinostat (SAHA) are quite promising combination therapy agents applied to the clinical treatment of cancer. In this study, we designed and synthesized a series of novel SN38-SAHA co-prodrugs, which were conjugated by four different amino acids including glycine, alanine, aminobutyric acid, and 6-aminocaproic acid. The hydrolytic reconversion rate to SN38 and SAHA critically depended on the carbon chain length, which were evaluated in PBS (pH 6.0/7.4) and plasma (human/mouse). With decreasing amino acid chain length, the hydrolytic reconversion rate increased gradually. The in vitro cytotoxicity test was evaluated by the sulforhodamine B (SRB) assay on the human lung adenocarcinoma cell line A549 and human colorectal cancer cell line HCT116. With the evaluation of stability and in vitro cytotoxicity, an appropriate linker was found, and the active drug can be released efficiently from compound 3a, which exhibited strong antiproliferative activity in A549 and HCT-116 cell lines correspondingly. These results indicated that the well-designed co-prodrug 3a and this kind of strategy can be a promising approach for anticancer therapy. |
| WOS关键词 | HISTONE DEACETYLASE INHIBITORS ; SUBEROYLANILIDE HYDROXAMIC ACID ; DNA TOPOISOMERASE-I ; BIOLOGICAL EVALUATION ; ESTER PRODRUGS ; PHASE-I ; SN-38 ; HDAC ; MECHANISMS ; DELIVERY |
| 资助项目 | Shanghai Science and Technology Council[16DZ2280100] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000507578300038 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/282442]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Qiumeng; Chen, Yi; Lu, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Sch Chem & Mol Engn, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Shuangxi,Hu, Zonglong,Zhang, Qiumeng,et al. Co-Prodrugs of 7-Ethyl-10-hydroxycamptothecin and Vorinostat with in Vitro Hydrolysis and Anticancer Effects[J]. ACS OMEGA,2020,5(1):350-357. |
| APA | Liu, Shuangxi,Hu, Zonglong,Zhang, Qiumeng,Zhu, Qiwen,Chen, Yi,&Lu, Wei.(2020).Co-Prodrugs of 7-Ethyl-10-hydroxycamptothecin and Vorinostat with in Vitro Hydrolysis and Anticancer Effects.ACS OMEGA,5(1),350-357. |
| MLA | Liu, Shuangxi,et al."Co-Prodrugs of 7-Ethyl-10-hydroxycamptothecin and Vorinostat with in Vitro Hydrolysis and Anticancer Effects".ACS OMEGA 5.1(2020):350-357. |
入库方式： OAI收割
来源：上海药物研究所
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