In silico and in vitro anti-inflammatory evaluation of 2,6-bis-(3'-ethoxy, 4'-hydroxybenzylidene)-cyclohexanone, 2,6-bis-(3'-Bromo,4'-methoxybenzylidene)-cyclohexanone, and 2,6-bis-(3',4'-dimethoxybenzylidene)-cyclohexanone

The aim of this research is to design the new mono-carbonyl analogs of curcumin, synthesize the molecules, and determine its activity in cyclooxygenase inhibition in vitro and in silico. New design MACs were performed by the Quantitative Structure-Activity Relationship (QSAR) study using the BuildQSAR program. 2,6-bis-(3-ethoxy, 4-hydroxybenzylidene)-cyclohexanone, 2,6-bis-(3-Bromo, 4-methoxybenzylidene)-cyclohexanone, and 2,6-bis-(3,4-dimethoxybenzylidene)-cyclohexanone had been synthesized using aldol condensation reaction. The anti-inflammatory assay was performed to measure the level of malondialdehyde. In silico studies were carried out to evaluate the activity of cyclooxygenase inhibition in cyclooxygenase-1 and cyclooxygenase-2 specific proteins. Molecular operating environment program was used for protocol docking. The results of the QSAR study reveal the good relationship of anti-inflammatory activities. The in vitro anti-inflammatory activities of 6-bis-(3-ethoxy, 4-hydroxybenzylidene)-cyclohexanone, 2,6-bis-(3-Bromo, 4-methoxybenzylidene)-cyclohexanone, and 2,6-bis-(3,4-dimethoxybenzylidene)-cyclohexanone indicate the promising potential to inhibit cyclooxygenase enzyme with IC<inf>50</inf> 13.53 μM, 11.56 μM, and 20.52 μM, respectively. The in silico evaluation showing that O atoms (47, from ketones) of 2,6-bis-(3-Bromo, 4-methoxybenzylidene)-cyclohexanone interact with ARG120 and TYR355 through H acceptor. © 2020 Elsevier B.V., All rights reserved.