Synthesis, molecular docking and anticancer activity of 5,5′-(phenylmethylene)bis(6-amino-2-thiouracil) derivatives

A series of 5,5 '-(phenylmethylene)bis(6-amino-2-thiouracil) derivatives (1-13) were synthesized by the condensation of 6-amino-2-thiouracil and benzaldehyde derivatives under reflux in glacial acetic acid. Nine compounds (3, 5 and 7-13) were novel. Good binding affinity (BE) in the active site of Eg5 was shown by all compounds, which ranged between -5.0 kcal mol(-1) to -26.7 kcal mol(-1). Most compounds in the series exhibited a stronger interaction than 5-fluorouracil (BE = -8.0 kcal mol(-1)) with Eg5. The docking results were supported by cytotoxicity studies of the synthesized compounds against HeLa (cervical cancer) cell lines, where all compounds exhibited better anti-cancer activity than 5-fluorouracil (IC50 = 12.08 mu g mL(-1)) at the lowest concentration (10 mu g mL(-1)) with IC50 values ranging from 4.18 to 10.20 mu g mL(-1).