Study on Interaction Between 5‐(4 Methoxyphenyl)‐1‐Phenyl‐1H‐1,2,3‐Triazole with High‐Abundant Blood Proteins and Identification of Low‐Abundant Proteins by Serum Proteomics

A comprehensive strategy, including spectroscopic, molecular simulation, proteomics, and bioinformatics techniques, was employed to investigate a novel triazole, 5-(4-methoxyphenyl)-1-phenyl-1H-1,2,3-triazole, its interactions with high-abundance blood proteins, and identification of low-abundance proteins. The binding constants and thermodynamic parameters of the triazole to two high-abundance blood globular proteins, human serum albumin, and human immunoglobulin G (HIgG), were obtained by spectroscopic techniques and computational chemistry. The two-dimensional gel electrophoresis in combination with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was employed to isolate and identify differentially expressed low-abundance proteins in human blood serum samples following exposure to the triazole. The results indicated that there is strong binding of the triazole to human serum albumin/HIgG and hydrophobic interaction plays a main role in the system. There were 21 highly expressed proteins identified from blood serum samples intervened by the triazole. By bioinformatics analysis, one of the differential proteins, kininogen-1 protein, was to explore the mechanism of action of 5-(4-methoxyphenyl)-1-phenyl-1H-1,2,3-triazole intervention on the kallikrein-kinin signaling pathways related to HeLa cervical cancer cells. The triazole displayed antiproliferative activity and significantly altered a kallikrein-10 expression, suggesting a possible antitumor mechanism involving the kallikrein-kinin system. These research findings provide scientific insights for further development and application of the 1,2,3-triazole compound. The study highlights the potential of the compound as a multifunctional pharmaceutical agent, particularly in cancer therapies, and lays the foundation for its future clinical applications in targeting drug-protein interactions.