Human topoisomerase II alpha (TopoIIα) is an enzyme involved in maintaining genomic integrity during the process of DNA replication and mitotic division. It is a vital therapeutic target for designing novel anticancer agents in targeted cancer therapy. 

In the present work, a series of sulfones was selected to evaluate their inhibitory activity against TopoIIα using computational approaches. Molecular docking results revealed that several sulfone analogs bind efficiently to the ATPase domain of TopoIIα. Among several sulfones screened, six sulfones exhibit higher binding affinity than the known TopoIIα inhibitor, salvicine.

According to the experimental results, it is suggested that sulfones could possibly have inhibitory potential against TopoIIα. Altogether, this is the first report shading light on the inhibitory activity of sulfones against TopoIIα, which will be useful for the design and development of new drugs targeting TopoIIα.

Kanika Verma, Panupong Mahalapbutr, Atima Auepattanapong, Onnicha Khaikate, Chutima Kuhakarn, Kaito Takahashi and Thanyada Rungrotmongkola* “Molecular dynamics simulations of sulfone derivatives in complex with DNA topoisomerase IIa ATPase domain” Journal of Biomolecular Structure and Dynamics 2020, doi: 10.1080/07391102.2020.1831961