Background: Prostaglandins are a family of eicosanoids biosynthesized from arachidonic
acid through cyclooxygenase (COX) pathway. Two isoforms of COX are well established:
COX-1, COX-2. Evidence supports the notion that cyclooxygenase-2, plays a crucial role in some
pathological conditions such as inflammation and cancer.
Objective: A new group of 1,3-diphenyl-3-(phenylamino)propan-1-ones was designed and synthesized
to investigate for their COX-2 inhibitory activity and inhibition of platelet aggregation.
Method: Docking study was performed using AutoDock vina software. In vitro COX-1 and COX-
2 isozyme inhibition studies were accomplished to obtain structure activity relationship data. The
in vitro antiplatelet aggregation activity was determined by turbidimetric procedure.
Results: In vitro COX inhibition assay showed that except compound 8c, all derivatives were selective
COX-2 inhibitors with IC50 values in the potent 0.20-0.35 µM range with high COX-2 selectivity
indexes (SI). Molecular modeling and docking studies indicated that synthesized compounds
had a binding similar to that of the known inhibitor SC-558 and the SO2Me group was inserted
into the COX-2 secondary pocket (Val523, Phe518, Ile517, Arg513 and His90) and C=O of the
central α, β-unsaturated-carbonyl moiety was oriented toward the entrance to the COX-2 binding
site (Tyr355 and Arg120).
Conclusion: The 1,3-diphenyl-3-(phenylamino)propan-1-ones are novel COX-2 inhibitors with
good COX-2 inhibitory and low affinity for COX-1 isoenzyme. Also our results demonstrated that
majority of these compounds inhibited AA-induced platelet aggregation.