Molecular Docking Studies of Schiff Bases with Azetidinone Against Dihydrofolate Reductase Enzyme as Potential Anti-cancer Agents

Abstract

Background: In recent times, cancer has emerged as a major health concern. It was established that every
antagonist of the dihydrofolate reductase exhibits anti-cancer activity. For anti-cancer action, several Schiff-based
derivatives with azetidinone rings were designed and docked against the dihydrofolate reductase protein (PDB
id:6CXK) in the current work. The ligands were compared to those of standard antagonists of dihydrofolate
reductase, that is, trimethoprim and pyrimethamine. Materials and Methods: The ligands were drawn in.mol
format using ChemSketch software and converted to.pdb format using Avogadro software. The iGEMDOCK
software was utilized to conduct molecular docking investigations, and Discovery Studio Visualizer was ultimately
used to visualize the results. Results and Discussion: Most compounds have demonstrated a better affinity for
binding to the dihydrofolate reductase. Most of the ligands have demonstrated nearly the same binding affinities
as that of the standard dihydrofolate reductase, such as trimethoprim (−102.1 kcal/mol) and pyrimethamine
(−91.8 kcal/mol). The top 2 compounds 3A8B (−100.6 kcal/mol) and 3A9B (−94.6 kcal/mol) were chosen for
visualization. Conclusion: Schiff base derivatives with azetidinone ring have the potential to be a promising
class of drugs for the treatment of anti-cancer action since they have a higher binding affinity to the dihydrofolate
reductase than standard antagonists.