Molecular Modelling, Synthesis and Evaluation of Flavone and Flavanone Scaffolds as Anti-inflammatory Agents.

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), HF_d (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 HFA_d (7-hydroxy-2-(thiophen-2-yl)-2,3- dihydro-4H-chromen-4-one) showed significant anti-inflammatory activity compared to the standard COX-2 inhibitors.

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.