Study of the structure-bioactivity of fleximers: synthesis, crystal structure, Hirshfeld surface analysis, and anti-inflammatory assays

Abstract

Synthesized and natural pyridones/pyridines derivatives exhibiting diverse biological activities. 2-pyridone has lactam-lactim tautomerization like thymine and uracil bases. In this study, COX-2 target based series of pyridone/pyridine linked fleximers were designed, synthesized and studied. All analogues binding affinity with COX-2 active site were studied through molecular docking, and anti-inflammatory activity studied by in vivo analysis. Weak interactions were studied to find binding sites among analogues through crystal packing, Hirshfeld surface analysis and in silico analysis. All the analogues exhibited anti-inflammatory activity, while compound (3) is the most active analogue among the series. In contrast, since compound (3) is a pyridine-phthalimide ring-containing analogue, the presence of a phthalimide group probably favors anti-inflammatory activity over other types of rings. The results suggested further investigations on compounds as anti-inflammatory prodrugs.