An in Silico Study: Searching for Potential Anti-Cancer Agents from Xanthone Derivatives Targeting Topoisomerase II-Alpha Protein

Cancer is one of the leading causes of death globally, which results in 10 million deaths in 2020 [1]. Besides advanced chemotherapeutic treatments, target-based strategies of cancer therapy are still proving to be overpowered effectively in drug research and development. One of the popular biological targets is the selective inhibition of Topoisomerase IIα, a gyrase DNA that reduces topological strain by its ability to cleavage and reseal double-strand DNA during replication, transcription, chromosome segregation, and recombination. In malignant cells, the concentration of Topoisomerase IIα is stronger and less reliant on the cell's state of proliferation [2]. Studies on xanthone compounds show outstanding antitumor activity. This prompted Molecular Docking and Pharmacophore Modeling studies of 2993 xanthone compounds on Topoisomerase IIα targets. The standard compound used in the study is the anti-cancer clinical drug etoposide, which acts on the TOP2A target. As a result, a single compound labeled 2905 was evaluated as a hit compound in cancer therapy through inhibiting topoisomerase IIα based on analyses of binding energy, binding efficiency, drug-like properties, toxicity, pharmacokinetics, and pharmacophore models.