中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Discovery of Novel SIRT1/2 Inhibitors with Effective Cytotoxicity against Human Leukemia Cells

文献类型：期刊论文

作者Cai, Haiyan1,2; Wang, Yingying2,3; Zhang, Jing2; Wei, Zhenquan2; Yan, Teng2; Feng, Chenxi2; Xu, Zhijian4; Zhou, Aiwu2; Wu, Yingli2,3
刊名JOURNAL OF CHEMICAL INFORMATION AND MODELING
出版日期2023-07-24
页码11
ISSN号1549-9596
DOI10.1021/acs.jcim.3c00556
通讯作者Cai, Haiyan(hanyezi@163.com) ; Wu, Yingli(wuyingli@shsmu.edu.cn)
英文摘要The sirtuin enzyme family members, SIRT1 and SIRT2, playboth tumor-promotingand tumor-suppressing roles, depending on the context and experimentalconditions. Compounds that inhibit either SIRT1 or SIRT2 show promisingantitumor effects in several types of cancer models, both in vitro and in vivo. The simultaneousinhibition of SIRT1 and SIRT2 is helpful in treating cancer by completelyblocking p53 deacetylation, leading to cell death. However, only afew SIRT1/2 dual inhibitors have been developed. Here, we report thediscovery of a novel series of SIRT1/2 dual inhibitors via a rationaldrug design that involved virtual screening and a substructure search.Eleven of the derived compounds exhibited high inhibitory activities,with IC50 < 5 & mu;M and high specificity for bothSIRT1 and SIRT2. Compounds hsa55 and PS9 strongly induced apoptosisand showed antiproliferative effects against human leukemia cell lines,which could be due to their ability to increase of p53 and & alpha;-tubulinacetylation, as we observed in MOLM-13 cells. Therefore, the new scaffoldsof these compounds and their efficacy in leukemia cell lines provideimportant clues for the further development of novel anti-leukemiadrugs.
WOS关键词SMALL-MOLECULE INHIBITOR ; NF-KAPPA-B ; P53 ACETYLATION ; SIRTUINS ; DEACETYLATION ; MECHANISM ; SURVIVAL ; DISEASES ; ANALOGS ; POTENT
资助项目National Natural Science Foundation of China National Natural Science Foundation of China[81870309] ; National Natural Science Foundation of China National Natural Science Foundation of China[32070934] ; National Natural Science Foundation of China National Natural Science Foundation of China[82170145] ; CAMS Innovation Fund for Medical Sciences (CIFMS)[2019-I2M-5-051] ; Shanghai Science and Technology Commission[20JC1410100] ; Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases ; State Key Laboratory of Oncogenes and Related Genes[KF2107] ; Shanghai jiaotong University school of medicine[2019HX008]
WOS研究方向Pharmacology & Pharmacy ; Chemistry ; Computer Science
语种英语
WOS记录号WOS:001034941300001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/306767]  
专题中国科学院上海药物研究所
通讯作者Cai, Haiyan; Wu, Yingli
作者单位1.Tongji Univ, Shanghai East Hosp, Dept Hematol, Sch Med, Shanghai 200120, Peoples R China
2.Shanghai Jiao Tong Univ, Key Lab Cell Differentiat & Apoptosis, Chinese Minist Educ, Sch Med, Shanghai 200025, Peoples R China
3.Shanghai Tongren Hosp, Hongqiao Int Inst Med, Fac Basic Med, Shanghai 200025, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Cai, Haiyan,Wang, Yingying,Zhang, Jing,et al. Discovery of Novel SIRT1/2 Inhibitors with Effective Cytotoxicity against Human Leukemia Cells[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING,2023:11.
APA Cai, Haiyan.,Wang, Yingying.,Zhang, Jing.,Wei, Zhenquan.,Yan, Teng.,...&Wu, Yingli.(2023).Discovery of Novel SIRT1/2 Inhibitors with Effective Cytotoxicity against Human Leukemia Cells.JOURNAL OF CHEMICAL INFORMATION AND MODELING,11.
MLA Cai, Haiyan,et al."Discovery of Novel SIRT1/2 Inhibitors with Effective Cytotoxicity against Human Leukemia Cells".JOURNAL OF CHEMICAL INFORMATION AND MODELING (2023):11.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。