1,2,3-Triazole-Based New Aurones as Anticancer Agents with the Capability to Target Extracellular Digestive Enzymes

This study involves the synthesis of a series of dimethyl substituted novel aurones, featuring 1,2,3-triazole as an integral structure. All the newly synthesized compounds were thoroughly characterized using various spectroscopic tools and also subjected to computational analysis utilizing the DFT/B3LYP methodology, which involved the determination of frontier molecular orbital energy values and the computation of various quantum chemical parameters. Further their impact on cell viability and cytotoxic activity on the adenocarcinoma gastric cell line (AGS) was investigated using cell-based MTT assay. Compounds 6d, 6o and 6p displayed significant cytotoxic activity, reducing cell viability to a greater extent with IC₅₀ values of 9.74, 20.09, and 5.92 µM, respectively and even better than the standard chemotherapeutic drug leucovorin (IC₅₀ = 30.8 µM). In addition, all the compounds were also screened for their extracellular enzymatic assay and through in vitro results compound 6n emerged as the efficient inhibitor of amylase (% inhibition = 51.92) and trypsin (% inhibition = 68.36), whereas an activation is observed for lipase (% activation = 269.48). In silico molecular docking was also conducted to assess the interactions between proteins and ligands, revealing the binding patterns of the synthesized compounds and the standard drug with receptor proteins.