Theoretical study and application of 2-phenyl-1,3,4-thiadiazole derivatives with optical and inhibitory activity against SHP1

doi:10.1039/d1cp04268h

	Theoretical study and application of 2-phenyl-1,3,4-thiadiazole derivatives with optical and inhibitory activity against SHP1
	Zhang, Chun 1; Sun, Yi-Tao 1; Gao, Li-Xin 1,2; Feng, Bo 1,2; Yan, Xue 1; Guo, Xue-Hui 3; Ren, Ai-Min 3; Zhou, Yu-Bo 2,4; Li, Jia 2,4; Wang, Wen-Long 1
刊名	PHYSICAL CHEMISTRY CHEMICAL PHYSICS
	2021-12-02
页码	14
ISSN号	1463-9076
DOI	10.1039/d1cp04268h
通讯作者	Ren, Ai-Min(aimin_ren@yahoo.com) ; Li, Jia(jli@simm.ac.cn) ; Wang, Wen-Long(wwenlong2011@163.com)
英文摘要	Src homology-2 domain-containing protein tyrosine phosphatase 1 (SHP1) is mainly restricted to hematopoietic and epithelial cells and widely accepted as a convergent node for oncogenic cell-signaling cascades. The development of efficient methods for rapidly tracing and inhibiting the SHP1 activity in complex biological systems is of considerable significance for advancing the integration of diagnosis and treatment of the related disease. With this aim, we designed and synthesized five 2-phenyl-1,3,4-thiadiazole derivatives (PT2, PT5, PT8, PT9 and PT10) here based on the reported SHP1 inhibitors (PT1, PT3, PT4, PT6 and PT7). The photophysical properties and inhibitory activities of these 2-phenyl-1,3,4-thiadiazole derivatives (PT1-PT10) against SHP1 were thoroughly studied from the theoretical simulation and experimental application aspects. The representative compound PT10 exhibited a larger quantum yield than the other molecules because of the smaller geometric relaxation and reorganization energy of the excited state, which was consistent with the results from the fluorescence experiments in organic solvents. In addition, PT10 showed a selective fluorescence response for SHP1 activity and low cytotoxicity in HeLa cells. Lastly, it indicated the potential application in two-photon cell fluorescence imaging in the future according to the calculated excellent two-photon absorption properties. In this contribution, firstly, we offered the fluorescent and activated molecule PT10 against SHP1, which achieved the integration of visualization and inhibitory activity of SHP1 preliminarily at the enzyme molecular level.
资助项目	National Natural Science Foundation of China[81773779] ; National Natural Science Foundation of China[21772068] ; Natural Science Foundation of Jiangsu Province[BK20190608] ; Fundamental Research Funds for the Central Universities[JUSRP121065] ; High Level Personnel Project of Jiangsu Province[JSSCBS20210848]
WOS关键词	2-PHOTON FLUORESCENT-PROBE ; LIVING CELLS ; ABSORPTION ; MOLECULES ; CONSTRUCTION ; EFFICIENCY ; DESIGN ; TARGET ; CANCER ; SERIES
WOS研究方向	Chemistry ; Physics
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000730290700001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/299199]
专题	中国科学院上海药物研究所
通讯作者	Ren, Ai-Min; Li, Jia; Wang, Wen-Long
作者单位	1.Jiangnan Univ, Sch Pharmaceut Sci, Wuxi 214122, Jiangsu, Peoples R China 2.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Jilin Univ, Coll Chem, Inst Theoret Chem, Liutiao Rd 2, Changchun 130061, Peoples R China 4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Chun,Sun, Yi-Tao,Gao, Li-Xin,et al. Theoretical study and application of 2-phenyl-1,3,4-thiadiazole derivatives with optical and inhibitory activity against SHP1[J]. PHYSICAL CHEMISTRY CHEMICAL PHYSICS,2021:14.
APA	Zhang, Chun.,Sun, Yi-Tao.,Gao, Li-Xin.,Feng, Bo.,Yan, Xue.,...&Wang, Wen-Long.(2021).Theoretical study and application of 2-phenyl-1,3,4-thiadiazole derivatives with optical and inhibitory activity against SHP1.PHYSICAL CHEMISTRY CHEMICAL PHYSICS,14.
MLA	Zhang, Chun,et al."Theoretical study and application of 2-phenyl-1,3,4-thiadiazole derivatives with optical and inhibitory activity against SHP1".PHYSICAL CHEMISTRY CHEMICAL PHYSICS (2021):14.