Chalcone Derivatives Targeting DNA Gyrase and DHFR Macromolecular Enzymes: A Comparative Molecular Docking Study

The aim of this work is to evaluate the efficiency of two newly prepared chalcones against several types of bacterial theoretically. We have synthesized M1 and M2 chalcones as macromolecule derivatives using Claisen Schmidt condensation, then compounds characterized via spectroscopic techniques; 1 H‐NMR, 13 C‐NMR, FTIR, and mass spectroscopy. Evaluation method of M1 and M2 antibacterial features has been carried out by molecular docking via MOE‐2014 against Staphylococcus aureus DNA gyrase (PDB: 2XCT) and Escherichia coli dihydrofolate reductase (PDB: 1RX2), as well as human dihydrofolate reductase (PDB: 1U72). The results demonstrated that synthesized chalcones macromolecules have high binding affinities (−5.25 to −7.23 kcal/mol) compared to reference antibiotic used in this work (ciprofloxacin and trimethoprim), and binding was better than plant metabolites such as thymol and eugenol. The presence of hydrogen bond with interaction of compounds in active site revealed good interactions which lead to suggest that these new chalcones have promised properties to develop for using as antibacterial agents after more investigations.