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Evodiamine-Inspired Topoisomerase-Histone Deacetylase Dual Inhibitors: Novel Orally Active Antitumor Agents for Leukemia Therapy br

文献类型：期刊论文

作者Wu, Shanchao3; Huang, Yahui3; Wang, Ting1,2; Li, Keliang3; Lu, Junjie3; Huang, Min1,2; Dong, Guoqiang3; Sheng, Chunquan3
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2022-03-24
卷号65期号:6页码:4818-4831
ISSN号0022-2623
DOI10.1021/acs.jmedchem.1c02026
通讯作者Wu, Shanchao(wushanchao072@smmu.edu.cn) ; Sheng, Chunquan(shengcq@smmu.edu.cn)
英文摘要On the basis of the synergism of topoisomerase (Top)and histone deacetylase (HDAC) inhibitors in antitumor therapy, a series of novel Top/HDAC dual inhibitors were designed and synthesized by the pharmacophore fusion strategy. After systematic structure-activity relationship studies, lead compound16jwasidentified to simultaneously inhibit both Top and HDAC with good potency, which showed potent antiproliferative activities with a broad spectrum. Mechanistic studies indicated that compound16jefficientlyinduced apoptosis with S cell-cycle arrest in HEL cancer cells. It wasorally active in HEL xenograft models and exhibited excellent in vivo antitumor efficacy (TGI = 68.5%; 10 mg/kg). Altogether, this work highlights the therapeutic potential of evodiamine-inspired Top/HDAC dual inhibitors and provides a valuable lead compound for the development of novel antitumor agents for leukemia therapy
WOS关键词CANCER ; POLYPHARMACOLOGY ; DESIGN ; DERIVATIVES ; CHALLENGES ; DISCOVERY
资助项目National Natural Science Foundation of China[21807113] ; National Natural Science Foundation of China[22077138] ; National Natural Science Foundation of China[81872742] ; National Natural Science Foundation of China[81725020]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000790749000024
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/301086]  
专题中国科学院上海药物研究所
通讯作者Wu, Shanchao; Sheng, Chunquan
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
3.Second Mil Med Univ, Sch Pharm, Dept Med Chem, Shanghai 200433, Peoples R China
推荐引用方式
GB/T 7714		 Wu, Shanchao,Huang, Yahui,Wang, Ting,et al. Evodiamine-Inspired Topoisomerase-Histone Deacetylase Dual Inhibitors: Novel Orally Active Antitumor Agents for Leukemia Therapy br[J]. JOURNAL OF MEDICINAL CHEMISTRY,2022,65(6):4818-4831.
APA Wu, Shanchao.,Huang, Yahui.,Wang, Ting.,Li, Keliang.,Lu, Junjie.,...&Sheng, Chunquan.(2022).Evodiamine-Inspired Topoisomerase-Histone Deacetylase Dual Inhibitors: Novel Orally Active Antitumor Agents for Leukemia Therapy br.JOURNAL OF MEDICINAL CHEMISTRY,65(6),4818-4831.
MLA Wu, Shanchao,et al."Evodiamine-Inspired Topoisomerase-Histone Deacetylase Dual Inhibitors: Novel Orally Active Antitumor Agents for Leukemia Therapy br".JOURNAL OF MEDICINAL CHEMISTRY 65.6(2022):4818-4831.

入库方式： OAI收割

来源：上海药物研究所

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