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Updated: Jul 7, 2025
Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Novel imidazo[1,2,4] triazole derivatives: Synthesis, fluorescence, bioactivity for SHP1
Xue Yan1, Chun Zhang2, Li-Xin Gao3
1School of Life Sciences and Health Engineering, Jiangnan University, Jiangsu, 214122, China; School of Chemical and Material Engineering, Jiangnan University, Jiangsu, 214122, China.
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.
Insights
Researchers developed novel imidazo[1,2,4] triazole derivatives to inhibit Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1). Compound 5p shows potent SHP1 inhibition and fluorescence properties for potential cancer diagnostics and therapeutics.
Area of Science:
- Medicinal Chemistry
- Chemical Biology
- Biophysics
Background:
- The Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) is a key regulator in oncogenic cell signaling, making it a promising therapeutic target for cancer treatment.
- Developing tools to monitor and modulate SHP1 activity is crucial for advancing cancer diagnosis and therapy.
- Imidazo[1,2,4] triazole scaffolds offer potential for designing novel inhibitors with desirable properties.
Purpose of the Study:
- To design and synthesize novel imidazo[1,2,4] triazole derivatives with inhibitory activity and fluorescence properties against SHP1.
- To explore the photophysical properties and inhibitory potential of these compounds for SHP1 PTP.
- To evaluate the utility of these compounds in biological systems, including cellular imaging.
Main Methods:
- Synthesis of imidazo[1,2,4] triazole derivatives containing salicylic acid.
- Photophysical characterization, including fluorescence quantum yield (QY) and aggregation-caused quenching (ACQ) effect.
- In vitro inhibition assays against SHP1 PTP.
- Selectivity studies for Fe3+ ions and detection limit determination.
- Cellular imaging experiments to assess biocompatibility and imaging potential.
Main Results:
- A series of imidazo[1,2,4] triazole derivatives (5a-5y) were synthesized and evaluated.
- Compound 5p demonstrated significant SHP1 PTP inhibitory activity (85.21 ± 5.17% at 100 μM) and notable fluorescence properties (QY = 0.37).
- Compound 5p exhibited an ACQ effect, high selectivity for Fe3+ ions, good anti-interference, and a low detection limit (5.55 μM).
- Cellular imaging studies confirmed the biocompatibility and potential of compound 5p for biological imaging.
Conclusions:
- Novel imidazo[1,2,4] triazole derivatives were successfully developed as potential SHP1 inhibitors.
- Compound 5p shows promise as a dual-function molecule for SHP1 inhibition and fluorescent detection.
- This study presents a viable strategy for creating fluorescent probes with bioactivity for SHP1, aiding in cancer research and drug development.
