Synthesis and bioactivity studies of covalent inhibitors derived from (-)-Chaetominine

doi:10.1016/j.molstruc.2021.130694

	Synthesis and bioactivity studies of covalent inhibitors derived from (-)-Chaetominine
	Zhou, Xian 1,3,4; Feng, Xuexin 2,3,4,6; Wang, Dachi 3,4; Chen, Deheng 3,4,5; Wu, Gaoxing 3,4,5; Yan, Ziqin 3,4; Lyu, Xilin 3,4; Wang, Huan 3,4,8; Yang, Jin-Ming 2,6; Zhao, Yujun 1,3,4,5,7
刊名	JOURNAL OF MOLECULAR STRUCTURE
	2021-10-05
卷号	1241 页码:14
关键词	Chaetominine Cellular growth inhibition Cancer cell line Covalent warhead
ISSN号	0022-2860
DOI	10.1016/j.molstruc.2021.130694
通讯作者	Yang, Jin-Ming(chemyjm@163.com) ; Zhao, Yujun(yjzhao@simm.ac.cn)
英文摘要	We reported herein the synthesis and bioactivity studies of compounds derived from the natural product (-)-Chaetominine (6). The key feature of these compounds is the incorporation of electrophilic groups that are capable of forming covalent bonds with the cysteine or threonine residues of cellular proteins. The cell growth inhibition activities of these derivatives of 6 were tested in four cancer cell lines, i.e. a leukemia cell line K562, a multiple myeloma cell line MM1.S, an acute myeloid leukemia cell line MV4-11, and a colon cancer cell line RKO. The data show that cellular growth inhibition IC50 values of 29 , an acrylamide-containing molecule, are 9-17 folds more potent than that of 6 , while other acrylamide-containing compounds are much less potent, suggesting 29 might have covalent interactions with cellular target proteins. Collectively, incorporation of an acrylamide moiety into 6 is a good strategy to improve its cell growth inhibition activity in cancer cell lines. (C) 2021 Elsevier B.V. All rights reserved.
资助项目	National Natural Science Foundation of China[82073682] ; National Natural Science Foundation of China[81872724] ; National Natural Science Foundation of China[81903429] ; National Major Science & Technology Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-004-010] ; Science and Technology Commission of Shanghai Municipality[18431907100] ; K. C. Wong Education Foundation
WOS关键词	PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR ; PHASE-II TRIAL ; SALINOSPORAMIDE-A ; ACTIVE-SITE ; DESIGN ; PX-866 ; DISCOVERY ; CETUXIMAB ; CDDO
WOS研究方向	Chemistry
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000670210200001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296848]
专题	中国科学院上海药物研究所
通讯作者	Yang, Jin-Ming; Zhao, Yujun
作者单位	1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 2.Yancheng Teachers Univ, Sch Pharm, Yancheng 224007, Jiangsu, Peoples R China 3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Small Mol Drug Res Ctr, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 5.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 6.Nanjing Univ Technol, Coll Chem Engn, Nanjing 211816, Peoples R China 7.Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China 8.Shanghai Tech Univ, Human Inst, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Xian,Feng, Xuexin,Wang, Dachi,et al. Synthesis and bioactivity studies of covalent inhibitors derived from (-)-Chaetominine[J]. JOURNAL OF MOLECULAR STRUCTURE,2021,1241:14.
APA	Zhou, Xian.,Feng, Xuexin.,Wang, Dachi.,Chen, Deheng.,Wu, Gaoxing.,...&Zhao, Yujun.(2021).Synthesis and bioactivity studies of covalent inhibitors derived from (-)-Chaetominine.JOURNAL OF MOLECULAR STRUCTURE,1241,14.
MLA	Zhou, Xian,et al."Synthesis and bioactivity studies of covalent inhibitors derived from (-)-Chaetominine".JOURNAL OF MOLECULAR STRUCTURE 1241(2021):14.