Synthesis and in Silico Evaluation of Novel Triazolone‐Derived Naphthalene‐2‐Sulfonates, Evaluation of Potential Antiproliferative Agents and Enzyme Inhibitory Activities

ABSTRACT This study reports the synthesis and biological evaluation of four novel N ‐acetyl‐derived heterocyclic compounds, namely 2‐((1‐acetyl‐3‐substituted‐5‐oxo‐1,5‐dihydro‐4H‐1,2,4‐triazol‐4‐yl)iminomethyl)‐phenyl‐naphthalene‐2‐sulfonates. The compounds were synthesized via acetylation reactions using acetic anhydride and were fully characterized by IR, 1 H NMR, 1 3 C NMR, elemental analysis, and HR‐MS techniques. The anticancer activities of the synthesized compounds were evaluated in the concentration range of 1.563–200 µM against HepG2 (hepatocellular carcinoma) and U87 (glioblastoma) cell lines, showing significant cytotoxic effects. Enzyme inhibition assays demonstrated potent inhibitory activities against α‐glucosidase, α‐amylase, acetylcholinesterase (AChE), and glutathione S‐transferase (GST), with IC 50 values ranging from 1.4 to 2.9 µM. Molecular docking studies, performed using DFT‐optimized geometries, supported the experimental findings and revealed strong and specific interactions with the target proteins. Among the studied derivatives, compound 2a exhibited the highest affinity toward α‐glucosidase, 2d showed superior binding to α‐amylase and AChE, while 2c demonstrated enhanced interaction with GST. Compound 2b displayed promising anticancer potential, forming stable complexes with proteins associated with the HepG2 and U87 cell lines.