Synthesis, Anticancer activity and molecular modelling of 2,6-bis-(4-nitrobenzylidene) cyclohexanone

Abstract

Bis(arylidene) cyclohexanone-based compound has been known for possessing various biological activity, especially as potential anticancer agent. The scaffold mimicking the structure of curcumin without the diketo group, thus eliminating the tautomeric group which could affect its potency. This study aimed to synthesize one of its derivate, 2,6-bis-(4-nitrobenzylidene) cyclohexanone and determine its anticancer activity against A549 pulmonary cancer cell line as well as its cytotoxicity against normal Vero cell. In addition, molecular docking study was performed to predict its binding mechanism in EGFR receptor. Synthesis was performed using aldol condensation with cyclohexanone and 4-nitrobenzaldehyde as starting material. This reaction was carried out in basic condition under microwave irradiation. Afterwards, the compound was tested its cytotoxic activity using MTT assay against A549 and Vero cell line. Ultimately, molecular docking was done using Vina 1.2.3. against EGFR receptor (PDB ID: 1M17). The results showed that 2,6-bis-(4-nitrobenzylidene) cyclohexanone has been successfully synthesized using this approach with acceptable yield. The compound also possesses anticancer activity against pulmonary cancer cell IC50 = 0.48±0.05mM) with negligible cytotoxicity against normal cell. Molecular docking result suggested that this compound targets EGFR receptor as it yielded low binding energy better than erlotinib, the natural ligand of EGFR. Further developments are needed to optimize its potency.