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Optimization of the Natural Product Calothrixin A to Discover Novel Dual Topoisomerase I and II Inhibitors with Improved Anticancer Activity

文献类型：期刊论文

作者Yang, Xiaohong1,2; Wang, Zhi-Peng1,2; Xiang, Sichuan1; Wang, Daoqiang3; Zhao, Yi4,5; Luo, Dong1; Qiu, Yanfei1; Huang, Chao1; Guo, Jian1; Dai, Yuanwei1
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2022-06-09
卷号65期号:11页码:8040-8061
ISSN号0022-2623
DOI10.1021/acs.jmedchem.2c00615
通讯作者Zhang, Shao-Lin(zhangsl@cqu.edu.cn) ; He, Yun(yun.he@cqu.edu.cn)
英文摘要Calothrixin A (CAA) is a dual Topo I and II inhibitor but exhibits poor antiproliferative activities and water solubility. Herein, a library of novel CAA analogues was synthesized. Among them, compound F16 exhibited superior water solubility (5 mg/mL) as compared to CAA (<5 mu g/mL). The mechanism of action studies confirmed that F16 acted as a dual Topo I and II poison. Furthermore, F16 displayed potent antiproliferative activities against high Topo I and II expression cell lines A375 and HCT116, with IC50 values of 20 and 50 nM, respectively. In xenograft models, F16 reduced the tumor growth at a dose of 10 or 20 mg/kg without apparent effect on the mouse weight, while the clinically used Topo II inhibitor VP-16 dramatically reduced the mouse weight. Collectively, our data demonstrated that F16 could be a promising lead for the development of novel dual Topo I and II antitumor agents.
资助项目National Natural Science Foundation of China[21807008] ; National Natural Science Foundation of China[22071012] ; National Natural Science Foundation of China[22001247] ; National Natural Science Foundation of China[22101036] ; Natural Science Foundation of Chongqing of China[cstc2020jcyj-msxmX0936] ; Natural Science Foundation of Chongqing of China[cstc2020jcyj-msxmX0650] ; Natural Science Foundation of Chongqing of China[cstc2020jcyj-msxmX0910] ; Natural Science Foundation of Chongqing of China[cstc2019jcyj-zdxmX0021] ; Fundamental Research Funds for the Central Universities[2020CDJ-LHZZ-008]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000810300800001
源URL[http://119.78.100.138/handle/2HOD01W0/16181]  
专题中国科学院重庆绿色智能技术研究院
通讯作者Zhang, Shao-Lin; He, Yun
作者单位1.Chongqing Univ, Sch Pharmaceut Sci, Chongqing Key Lab Nat Prod Synth & Drug Res, Chongqing 401331, Peoples R China
2.Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Chongqing 400714, Peoples R China
3.Chongqing Technol & Business Univ, Sch Environm & Resources, Chongqing 400067, Peoples R China
4.Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Chongqing 400714, Peoples R China
5.Chongqing Univ Technol, Sch Pharm & Bioengn, Chongqing 400054, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Xiaohong,Wang, Zhi-Peng,Xiang, Sichuan,et al. Optimization of the Natural Product Calothrixin A to Discover Novel Dual Topoisomerase I and II Inhibitors with Improved Anticancer Activity[J]. JOURNAL OF MEDICINAL CHEMISTRY,2022,65(11):8040-8061.
APA Yang, Xiaohong.,Wang, Zhi-Peng.,Xiang, Sichuan.,Wang, Daoqiang.,Zhao, Yi.,...&He, Yun.(2022).Optimization of the Natural Product Calothrixin A to Discover Novel Dual Topoisomerase I and II Inhibitors with Improved Anticancer Activity.JOURNAL OF MEDICINAL CHEMISTRY,65(11),8040-8061.
MLA Yang, Xiaohong,et al."Optimization of the Natural Product Calothrixin A to Discover Novel Dual Topoisomerase I and II Inhibitors with Improved Anticancer Activity".JOURNAL OF MEDICINAL CHEMISTRY 65.11(2022):8040-8061.

入库方式： OAI收割

来源：重庆绿色智能技术研究院

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