Development of coumarin and procaine linked hybrid molecules as a novel class of SHP1 fluorescent activators

  • Eur J Med Chem. 2025 Apr 15:288:117394. doi: 10.1016/j.ejmech.2025.117394.
Xu-Yang Mu  1 ,  Li-Xin Gao  2 ,  Zhen-Xuan Zhang  3 ,  Zi-Tong Cao  4 ,  Qing Cao  5 ,  Chun Zhang  5 ,  Jia Li  6 ,  Da-Jun Xiang  7 ,  Yu-Bo Zhou  8 ,  Wen-Long Wang  9
Affiliations
  • 1. School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, China; School of Chemical and Material Engineering, Jiangnan University, Wuxi, 214122, China.
  • 2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 3. School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan Tsuihang New District, Guangdong, 528400, China.
  • 4. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
  • 5. School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, China.
  • 6. Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan Tsuihang New District, Guangdong, 528400, China.
  • 7. Xishan People's Hospital of Wuxi City, Wuxi, Jiangsu, 214105, China. Electronic address: [email protected].
  • 8. Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan Tsuihang New District, Guangdong, 528400, China. Electronic address: [email protected].
  • 9. School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, China; School of Chemical and Material Engineering, Jiangnan University, Wuxi, 214122, China. Electronic address: [email protected].
PMID: 39987836 DOI: 10.1016/j.ejmech.2025.117394
Abstract

The development of small fluorescent organic molecules used in bioimaging experiment has boomed the progress of molecular and cellular biology, providing new and efficient tools to elucidate a myriad of cellular and multicellular processes. In this work, a class of fluorescent activators against SHP1 was designed and synthesized for the first time. The representative compound 3n showed activating effect against SHP1 with EC50 of 17.66 ± 1.48 μM and a fluorescence quantum yield of 0.521 in DMSO. Meanwhile, 3n showed good selectivity for SHP1, inhibited the proliferation of SU-DHL-2 cells and OCI-Ly10 cells with IC50 of 8.66 ± 1.26 μM and 9.16 ± 0.53 μM and exhibited potential for cellular imaging on human breast Cancer cells.

Keywords
Cellular imaging; Coumarin-procaine hybrid molecules; Fluorescent organic molecules; SHP1; Selectivity for SHP1 homologous proteins.
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