Potential inhibitors of Topoisomerase IIα identified by molecular docking

Inhibiting topoisomerase II by catalytic mechanism is one of the strategies for the development of new anticancer inhibitors of this enzyme. Since the anticancer effect of marketed topoisomerase II inhibitors was linked to the targeting of topoisomerase IIα, while inhibition of the ß isoform was responsible for secondary cancers induced by these inhibitors, we turned to the search for novel catalytic inhibitors of topoisomerase IIα using docking-based virtual screening methods. Docking was realized after validation with RMSD using the human protein Topoisomerase IIα ATPase domain by Molegro Virtual Docker 6.0 software.Curcumin is an antioxidant, anti-inflammatory, antimicrobial and plays a crucial role in the treatment of cancer. It has proved in silico the inhibition toward the site studied here, so, the database screened was constructed from similars of curcumin.Interpretation of the docking results was made regarding the natural substrate (ATP) and curcumin. Six hits selected from 724 molecules screened, gave satisfactory results in silico. These molecules have been shown to have better interaction energy than curcumin, as well as a better hydrogen bond energy. Two of them showed good interactions and good predicted physicochemical, pharmacokinetic, and toxicological properties and will be tested in vitr