Introduction:
Intermediate covalent complex of DNA-Topoisomerase II enzyme is the
most promising target of the anticancer drugs to induce apoptosis in cancer cells. Currently, anticancer
drug and chemotherapy are facing major challenges i.e., drug resistance, chemical instability
and, dose-limiting side effect. Therefore, in this study, natural therapeutic agents (series of
Ganoderic acids) were used for the molecular docking simulation against Human DNATopoisomerase
II beta complex (PDB ID:3QX3).
Methods:
Molecular docking studies were performed on a 50 series of ganoderic acids reported in
the NCBI-PubChem database and FDA approved anti-cancer drugs, to find out binding energy, an
interacting residue at the active site of Human DNA-Topoisomerase II beta and compare with the
molecular arrangements of the interacting residue of etoposide with the Human DNA topoisomerase
II beta. The autodock 4.2 was used for the molecular docking and pharmacokinetic and toxicity
studies were performed for the analysis of physicochemical properties and to check the toxicity effects.
Discovery studio software was used for the visualization and analysis of docked pose.
Results and Conclusion:
Ganoderic acids (GS-1, A and DM) were found to be a more suitable
competitor inhibitor among the ganoderic acid series with appropriate binding energy, pharmacokinetic
profile and no toxicity effects. The interacting residue (Met782, DC-8, DC-11 and DA-12)
shared a chemical resemblance with the interacting residue of etoposide present at the active site of
human topoisomerase II beta receptor.
QSAR and docking studies on xanthone derivatives for anticancer activity targeting DNA topoisomerase IIα
