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.
Jacalin is among the most thoroughly studied lectins. Its carbohydrate-binding site has also been well characterized. It has been postulated that the lower affinity of β-galactosides for jacalin compared with α-galactosides is caused by steric interactions of the substituents in the former with the protein. This issue has been explored energetically and structurally using different appropriate carbohydrate complexes of jacalin. It turns out that the earlier postulation is not correct. The interactions of the substituent with the binding site remain essentially the same irrespective of the anomeric nature of the substitution. This is achieved through a distortion of the sugar ring in β-galactosides. The difference in energy, and therefore in affinity, is caused by a distortion of the sugar ring in β-galactosides. The elucidation of this unprecedented distortion of the ligand as a strategy for modulating affinity is of general interest. The crystal structures also provide a rationale for the relative affinities of the different carbohydrate ligands for jacalin.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.