Repurposing of antitumor drug candidate Quisinostat lead to novel spirocyclic antimalarial agents

doi:10.1016/j.cclet.2020.12.0231001-8417/

	Repurposing of antitumor drug candidate Quisinostat lead to novel spirocyclic antimalarial agents
	Li, Ruoxi 1; Ling, Dazheng 1; Tang, Tongke2,5 ; Huang, Zhenghui 2; Wang, Manjiong 1; Mao, Fei 1; Zhu, Jin 1; Jiang, Lubin2,5 ; Li, Jian 1,3,4; Li, Xiaokang 1
	2021-05
发表期刊	CHINESE CHEMICAL LETTERS (IF:9.4[JCR-2023],7.3[5-Year])
ISSN	1001-8417
EISSN	1878-5964
卷号	32 期号:5 页码:1660-1664
DOI	10.1016/j.cclet.2020.12.0231001-8417/
摘要	Antimalarial chemotherapies endowed with effectiveness against drug-resistant parasites and good safety are urgently required in clinical. Our previous research revealed that clinical phase II antitumor drug Quisinostat was a promising antimalarial prototype by inhibiting the activity of Plasmodium falciparum (P. falciparum) histone deacetylase (PfHDAC). Herein, 30 novel spirocyclic linker derivatives were designed and synthesized based on Quisinostat as lead compound, and then their antimalarial activities and cytotoxicity were systematically evaluated. Among them, compounds 8 and 27 could effectively eliminate wild-type and multi-drug resistant P. falciparum parasites, and display weakened cytotoxicity and good metabolic stability. Western blot assay demonstrated that they could inhibit PfHDAC activity like Quisinostat. In addition, both 8 and 27 showed certain antimalarial efficacy in rodent malaria model, and the animal toxicity of 8 was significantly improved compared with Quisinostat. Overall, 8 and 27 were structurally novel PfHDAC inhibitors and provided prospective prototype for further antimalarial drug research. (c) 2021 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
关键词	Malaria PfHDAC inhibitor Drug repurposing Epigenetic modulator Erythrocytic therapy
收录类别	SCIE
语种	英语
WOS研究方向	Chemistry
WOS类目	Chemistry, Multidisciplinary
WOS记录号	WOS:000647702900011
出版者	ELSEVIER SCIENCE INC
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/126667
专题	生命科学与技术学院_特聘教授组_江陆斌组生命科学与技术学院_博士生
通讯作者	Jiang, Lubin; Li, Jian; Li, Xiaokang
作者单位	1.East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China; 2.Chinese Acad Sci, Univ Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China; 3.Dali Univ, Coll Pharm & Chem, Dali 671000, Peoples R China; 4.East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai 200237, Peoples R China; 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Ruoxi,Ling, Dazheng,Tang, Tongke,et al. Repurposing of antitumor drug candidate Quisinostat lead to novel spirocyclic antimalarial agents[J]. CHINESE CHEMICAL LETTERS,2021,32(5):1660-1664.
APA	Li, Ruoxi.,Ling, Dazheng.,Tang, Tongke.,Huang, Zhenghui.,Wang, Manjiong.,...&Li, Xiaokang.(2021).Repurposing of antitumor drug candidate Quisinostat lead to novel spirocyclic antimalarial agents.CHINESE CHEMICAL LETTERS,32(5),1660-1664.
MLA	Li, Ruoxi,et al."Repurposing of antitumor drug candidate Quisinostat lead to novel spirocyclic antimalarial agents".CHINESE CHEMICAL LETTERS 32.5(2021):1660-1664.