Design, synthesis and molecular docking studies of new azomethine derivatives as promising anti-inflammatory agents

Abstract

Herein, we synthesized a series of Ibuprofen-based 4a-k, quinoxaline-based 9a-f and pyridine-based 13a-h azomethine derivatives and studied their anti-inflammatory potency. The in-silico docking studies of the synthesized compounds 4a-k revealed better affinity for COX-2 as compared to COX-1 with best binding exhibited by 4a, 4d, and 4k.In vitro COX-1 and COX-2 inhibition assay performed on the azomethine derivatives further proved that synthesized compounds of series 4, 9 and 13 showed less inhibition of COX-1 enzyme than that of COX-2 enzyme. However, their SI values indicated that compounds had no COX-2 selectivity. The in-vivo screening of the selected compounds indicated compound 4d to be more potent exhibiting the best % inhibition of 70.70 ± 2.41, as compared to the standard NSAIDs. Based on the above observations, a well defined structure activity relationship analysis (SAR) has been described showcasing the importance of various functionalities for anti-inflammatory effects. Further, the azomethine derivatives have been found to be better superoxide radical scavengers with no significant DPPH activity. Due to their antioxidant properties, compounds were screened for their cytotoxicity against cervical cancer derived HeLa and breast cancer derived MCF-7 cell with the drug Paclitaxel as the standard. However, no significant cytotoxic effect was observed for the compounds. Also, the late apoptosis in cervical HeLa cancer cells did not show the expected results, as the compounds proved to be weakly cytotoxic. Thus, the major findings of the work demonstrates the Schiff bases to be promising anti-inflammatory agents compatible with NSAIDs, having moderate anti-oxidant properties with minimal cytotoxicity.