Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product

doi:10.3390/molecules24061059

	Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product
	Zhao, Hongchuan 4; Sun, Pu 1,2; Guo, Wei 1,2; Wang, Yi 1; Zhang, Ao 2,3,4; Meng, Linghua 1,2; Ding, Chunyong 2,4
刊名	MOLECULES
	2019-03-02
卷号	24 期号:6 页码:11
关键词	indoleamine 2 3-dioxygenase 1 immunosuppressive natural product ortho-naphthaquinone molecular docking
ISSN号	1420-3049
DOI	10.3390/molecules24061059
通讯作者	Meng, Linghua(lhmeng@simm.ac.cn) ; Ding, Chunyong(chding@simm.ac.cn)
英文摘要	There is great interest in developing small molecules agents capable of reversing tumor immune escape to restore the body's immune system. As an immunosuppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO-1) is considered a promising target for oncology immunotherapy. Currently, none of IDO-1 inhibitors have been launched for clinical practice yet. Thus, the discovery of new IDO-1 inhibitors is still in great demand. Herein, a series of diverse ortho-naphthaquinone containing natural product derivatives were synthesized as novel IDO-1 inhibitors. Among them, 1-ene-3-ketone-17-hydroxyl derivative 12 exhibited significantly improved enzymatic and cellular inhibitory activity against IDO-1 when compared to initial lead compounds. Besides, the molecular docking study disclosed that the two most potent compounds 11 and 12 have more interactions within the binding pocket of IDO-1 via hydrogen-bonding, which may account for their higher IDO-1 inhibitory activity.
资助项目	National Natural Science Foundation of China[21877120] ; National Natural Science Foundation of China[81430080] ; National Program on Key Basic Research Project of China[2015CB910603] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-010-001] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020320]
WOS关键词	DENDRITIC CELLS ; TANSHINONE I ; CONSTITUENTS ; DERIVATIVES ; SUPPRESSION ; CHEMISTRY
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI
WOS记录号	WOS:000465503800035
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/290050]
专题	中国科学院上海药物研究所
通讯作者	Meng, Linghua; Ding, Chunyong
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China 3.ShanghaiTech Univ, Sch Life Scienece & Technol, Shanghai 20120, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Hongchuan,Sun, Pu,Guo, Wei,et al. Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product[J]. MOLECULES,2019,24(6):11.
APA	Zhao, Hongchuan.,Sun, Pu.,Guo, Wei.,Wang, Yi.,Zhang, Ao.,...&Ding, Chunyong.(2019).Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product.MOLECULES,24(6),11.
MLA	Zhao, Hongchuan,et al."Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO-1) Inhibitors Based on Ortho-Naphthaquinone-Containing Natural Product".MOLECULES 24.6(2019):11.