Design, docking, synthesis, and characterization of novel N'(2-phenoxyacetyl) nicotinohydrazide and N'(2-phenoxyacetyl)isonicotinohydrazide derivatives as anti-inflammatory and analgesic agents

Abstract Inflammation is the complex biological response of vascular tissues, which is partly determined by prostaglandins (PLA2). The cyclooxygenase (COX) enzyme exists in two isoforms: COX-1 and COX-2 and by the action of this, the PGs are produced. Besides, nonsteroidal anti-inflammatory drugs (NSAIDs) are therapeutic agents useful in the treatment of inflammation. Encouraged by this, the new derivatives of N'(2-phenoxyacetyl)nicotinohydrazide 9(a-e) and N'(2-phenoxyacetyl)isonicotinohydrazide 10(a-e) were designed, synthesized, characterized, and identified as remarkable anti-inflammatory and analgesic agents. These compounds were prepared in a series of steps starting with different phenol derivatives. Among the series, compound (10e) showed the highest IC50 value for COX-1 inhibition, whereas compounds (9e) and (10e) exhibited the highest COX-2SI. Further, molecular Docking Studies have been performed for the potent compound to check the three-dimensional geometrical view of the ligand binding to the targeted enzymes.