Synthesis, Biological Evaluation and Docking Studies of N-substituted Resveratrol Derivatives.

A total of 19 resveratrol derivatives, including 12 imines and 7 amines, were synthesized, among which compounds 1, 5, 6, 7 ' , 11 ', and 13 are new compounds. The anti-inflammatory and antitumor activities of these compounds were evaluated in vitro. The results revealed that compounds 1, 6, 8 ', 12, and 12 ' exhibited significant inhibitory effects (> 50%) on NO production at the concentration of 10 mu M and their NO production inhibitory activities have a significant concentration-dependent ability. Additionally, compounds 8 ' and 12 ' showed promising COX-2 inhibitory activity, and the molecular docking analysis indicated their stable binding to multiple amino acid residues within the active pocket of COX-2 through hydrogen bonding. Moreover, compound 12 ' exhibited inhibitory effects on various tumor cell lines and induced apoptosis in MCF-7 breast cancer cells, which was not observed with resveratrol alone. Therefore, the N-substituted structural modification of resveratrol would have possibly enhanced the bioactivity of resveratrol and facilitated its application.