Interaction of an anticancer oxygenated propenylbenzene derivatives with human topoisomerase II α and actin: molecular modeling and isothermal titration calorimetry studies

Abstract Cancer diseases are one of the most common causes of death. It is important to reduce the proliferation of cancer cells at an early stage, but also to limit their migration. There is a need to find new compounds of moderate anticancer prevention activity for long administration. TOPIIα and actin are proteins that in states of inflammation can cause the progression of cancer and neoblastic cell migrations. Looking for compounds that will work comprehensively in preventing cancer, interacting with both TOPIIα and actin is crucial/was our aim. In this study, the antioxidant properties of propenylbenzene derivatives and their affinity to bind actin and TOPIIα causing inhibition of their functions were evaluated. The ligand–protein binding assay was carried out by isometric titration calorimetry (ITC), and molecular docking, and the antioxidant potential. The highest chelation activity was shown by 5b: 83.95% (FRAP 18.39 μmol Fe(II) mL −1 ). High affinity for actin and TOPIIα using ITC and docking was shown by diol forms. For actin the best ligands were 2b (∆H − 51.49 kJ mol −1 , ∆G − 27.37 kJ mol −1 ) and 5b (∆H − 17.25 kJ mol −1 , ∆G − 26.20 kJ mol −1 ), whereas for TOPIIα: 3b (∆H − 163.86 kJ mol −1 , ∆G − 34.60 kJ mol −1 ) and 5b (∆H − 160.93 kJ mol −1 , ∆G − 32.92 kJ mol −1 ). To confirm the occurrence of the interactions at the active site of the proteins, molecular docking and subsequent molecular dynamics simulations were performed, which showed for both actin and TOPIIα the highest enthalpy of interactions of 5b: − 34.94 kJ mol −1 and − 25.52 kJ mol −1 , respectively.