Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Carbazole-Based Carbohydrazone Derivatives

doi:10.6023/cjoc201907043

	Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Carbazole-Based Carbohydrazone Derivatives
	Li, Yingjun 1; Liu, Xuejie 1; Liu, Jihong 2; Gao, Lixin 3; Jin, Kun 4; Sheng, Li 3; Yang, Hongjing 1; Lin, Ledi 1; Li, Jia 3
刊名	CHINESE JOURNAL OF ORGANIC CHEMISTRY
	2020-02-25
卷号	40 期号:2 页码:478-488
关键词	carbohydrazone carbazole synthesis PTP1B inhibitor molecular docking DFT calculations
ISSN号	0253-2786
DOI	10.6023/cjoc201907043
通讯作者	Li, Yingjun(chemlab.lnnu@163.com) ; Li, Jia(jli@simm.ac.cn)
英文摘要	A series of novel carbazole-based mono-/bis-carbohydrazone derivatives 3 and 4 were synthesized. Their structures were characterized by H-1 NMR, C-13 NMR, IR spectra and elemental analysis. The inhibitory activities of all synthesized compounds against protein tyrosine phosphatase 1B (PTP1B) were evaluated, and the structure-activity relationship was discussed. The results indicated that most of the compounds had good inhibitory activity against PTPIB, and 1,5-bis[(9-butyl-3-carbazolypmethylene]carbohydrazone (4c) showed the highest inhibitory activity against PTP1B with IC50 =(4.81 +/- 0.41) mu mol/L and the activity was higher than that of the control drug oleanolic acid. Molecular docking and density functional theory (DFT) calculations of 3f and 4c were carried out. The results of molecular docking indicated that l-[(9-heptyl-3-carbazolyl)methylene]carbohydrazone (3t) and 4c bind to an active site of PTP1B enzyme formed by the helices alpha 3 and alpha 6, and formed a stable complex respectively with PTPIB enzyme by hydrogen bonds, polar, hydrophobic and pi-pi interactions.
资助项目	Natural Science Foundation of Liaoning Province[20102126]
WOS关键词	ANTICANCER ; COMPLEXES ; ANTIBACTERIAL ; ANTIOXIDANT ; THIOCARBOHYDRAZONE ; CR(III) ; FE(III) ; MN(II)
WOS研究方向	Chemistry
语种	英语
出版者	SCIENCE PRESS
WOS记录号	WOS:000522786900022
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280789]
专题	中国科学院上海药物研究所
通讯作者	Li, Yingjun; Li, Jia
作者单位	1.Liaoning Normal Univ, Coll Chem & Chem Engn, Dalian 116029, Peoples R China 2.Dalian Univ Technol, Chem Anal & Inspect Ctr, Dalian 116023, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 4.Dalian Univ Technol, State Key Lab Fine Chem, Dalian 116012, Peoples R China
推荐引用方式 GB/T 7714	Li, Yingjun,Liu, Xuejie,Liu, Jihong,et al. Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Carbazole-Based Carbohydrazone Derivatives[J]. CHINESE JOURNAL OF ORGANIC CHEMISTRY,2020,40(2):478-488.
APA	Li, Yingjun.,Liu, Xuejie.,Liu, Jihong.,Gao, Lixin.,Jin, Kun.,...&Li, Jia.(2020).Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Carbazole-Based Carbohydrazone Derivatives.CHINESE JOURNAL OF ORGANIC CHEMISTRY,40(2),478-488.
MLA	Li, Yingjun,et al."Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Carbazole-Based Carbohydrazone Derivatives".CHINESE JOURNAL OF ORGANIC CHEMISTRY 40.2(2020):478-488.