Eco‐Friendly Synthesis, Molecular Docking, and Anti‐Inflammatory Activities of Novel 3‐Cyanoquinoline Derivatives via Microwave Irradiation

Abstract In the present work, novel series of 3‐cyanoquinoline derivatives 4a–h were synthesized via one‐pot reaction of 2‐naphthaldehyde ( 1 ), malononitrile ( 2 ), ammonium acetate, and some phenol derivatives 3a–h using microwave irradiation (MWI). Excellent yields (89%–94%) were obtained, shorter reaction time (6–10 min), simple work, and to avoid any toxic solvents were the advantages of application of MWI. The structures of novel compounds 4a–h were confirmed via spectral data and elemental analysis. The anti‐inflammatory activities of new compounds were evaluated using the egg albumin denaturation method and compared with ibuprofen as a reference drug. Compounds 4a , 4b , 4c , and 4d exhibited significant anti‐inflammatory activities, with inhibition percentages from 80.80% to 87.76% at 500 µM, compared to ibuprofen (92.06%). Furthermore, the newly synthesized 3‐cyanoquinoline derivatives 4a–h were subjected to molecular docking simulations against the enzyme human cyclooxygenase‐2 (COX‐2), using tolfenamic acid as a reference ligand (PDB ID: 5IKT). The docking results revealed that the 3‐cyanoquinoline derivatives effectively interact with COX‐2, a pivotal enzyme in the inflammatory pathway.