Objective: The objective of the study was to develop new Cyclooxygenase-2 inhibitors as
anti-inflammatory agents from the synthetic route.
Materials and Methods: The 2-phenyl-4H-chromen-4-one and 2-phenyl-2,3-dihydro-4H-chromenone
hybrids were synthesised and characterised by using UV, IR, 1H-NMR, and mass spectrometry.
An attempt was made for consolidated lead flavones and flavanones scaffolds by determining ADME/
T properties. Molecular docking simulations were performed by using Autodock.4 to understand
the binding interaction over the targeted enzyme Cyclooxygenase-2. The titled compounds were
evaluated for various in-vitro models for antioxidant and anti-inflammatory activities and based upon
the IC50 values, the selected compounds were screened for in vivo anti-inflammatory activity by both
acute and chronic models.
Results and Discussion: Twenty titled compounds were synthesised and elucidated their structure
for confirmation of their functional groups by various spectroscopic techniques. Among the synthesized
compounds, flavone derivatives such as HFc (7-hydroxy-3-(4-methoxy phenyl)-4H-chromen-4-
one), HFd (2-(2,4-di methoxy-phenyl)-7-hydroxy-4H-chromen-4-one) and HFe (7-hydroxy-2-
(thiophen-2-yl)-4H-chromen-4-one) produced higher potency. Flavanone derivatives HFAc (7-
hydroxy-2-(4-hydroxy-3-methoxy phenyl)-2,3-dihydro-4H-chromen-4-one), HFAb (7-hydroxy-2-(4-
methoxy phenyl)-2,3-dihydro-4H-chromen-4-one) and HFAd (7-hydroxy-2-(thiophen-2-yl)-2,3-
dihydro-4H-chromen-4-one) showed significant anti-inflammatory activity compared to the standard
Conclusion: The flavone and flavanone scaffolds possess their excellent inhibitory action over the
Cyclooxygenase-2 and act as a potential anti-inflammatory agent. The results of computational studies
were also significantly correlated and concluded that those naturally mimicking flavonoid analogues
were tremendous candidates to fight against the inflammatory diseases in drug discovery.