2. Academic Validation
  3. Novel imidazo[1,2,4] triazole derivatives: Synthesis, fluorescence, bioactivity for SHP1

Novel imidazo[1,2,4] triazole derivatives: Synthesis, fluorescence, bioactivity for SHP1

  • Eur J Med Chem. 2024 Feb 5:265:116027. doi: 10.1016/j.ejmech.2023.116027.
Xue Yan 1,  Chun Zhang 2,  Li-Xin Gao 3,  Min-Min Liu 2,  Yu-Ting Yang 2,  Li-Jie Yu 2,  Yu-Bo Zhou 4,  Slieman Milaneh 5,  Yun-Long Zhu 6,  Jia Li 7,  Wen-Long Wang 8
Affiliations

Affiliations

  • 1 School of Life Sciences and Health Engineering, Jiangnan University, Jiangsu, 214122, China; School of Chemical and Material Engineering, Jiangnan University, Jiangsu, 214122, China.
  • 2 School of Life Sciences and Health Engineering, Jiangnan University, Jiangsu, 214122, China.
  • 3 School of Life Sciences and Health Engineering, Jiangnan University, Jiangsu, 214122, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 4 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 5 School of Life Sciences and Health Engineering, Jiangnan University, Jiangsu, 214122, China; Higher Institute of Applied Science and Technology, Department of Pharmaceutical and Chemical Industries, Damascus, 31983, Syria.
  • 6 Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, Jiangsu, 214002, China. Electronic address: [email protected].
  • 7 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: [email protected].
  • 8 School of Life Sciences and Health Engineering, Jiangnan University, Jiangsu, 214122, China; School of Chemical and Material Engineering, Jiangnan University, Jiangsu, 214122, China. Electronic address: [email protected].
PMID: 38128236 DOI: 10.1016/j.ejmech.2023.116027
Abstract

The Src homology 2 domain-containing protein tyrosine Phosphatase 1 (SHP1) is a convergent node for oncogenic cell-signaling cascades. Consequently, SHP1 represents a potential target for drug development in Cancer treatment. The development of efficient methods for rapidly tracing and modulating the SHP1 activity in complex biological systems is of considerable significance for advancing the integration of diagnosis and treatment of the related disease. Thus, we designed and synthesized a series of imidazo[1,2,4] triazole derivatives containing salicylic acid to explore novel scaffolds with inhibitory activities and good fluorescence properties for SHP1. The photophysical properties and inhibitory activities of these imidazo[1,2,4] triazole derivatives (5a-5y) against SHP1PTP were thoroughly studied from the theoretical simulation and experimental application aspects. The representative compound 5p exhibited remarkable fluorescence response (P: 0.002) with fluorescence quantum yield (QY) of 0.37 and inhibitory rate of 85.21 ± 5.17% against SHP1PTP at the concentration of 100 μM. Furthermore, compound 5p showed obvious aggregation caused quenching (ACQ) effect and had high selectivity for Fe3+ ions, good anti-interference and relatively low detection limit (5.55 μM). Finally, the cellular imaging test of compound 5p also exhibited good biocompatibility and certain potential biological imaging application. This study provides a potential way to develop molecules with fluorescent properties and bioactivities for SHP1.

Keywords

Bioactivity; Cellular imaging; Fluorescence property; Imidazo[1,2,4] triazole derivatives; SHP1.

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