Design, Microwave Synthesis, Antibacterial Activity, ADMET, and Photo Physical Analysis of 3-Styryl-2H-Chromene-Fused Maleimide Derivatives as Potential DNA Gyrase Inhibitors

In this study, a series of 18 3-styryl-2H-chromene-fused maleimide derivatives were synthesized and characterized by using ¹H NMR, ¹³C NMR, HRMS, and FT-IR spectroscopic techniques. Additionally, the crystal structure of compound 16k was confirmed by single-crystal X-ray diffraction analysis. In silico molecular docking studies were formed against bacterial strains Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis), revealing that the compound 16e exhibited the strongest binding affinities, with binding scores of −8.6 kCal/mol (E. coli) and −9.7 kCal/mol (E. faecalis). In vitro antibacterial evaluation further demonstrated that compound 16e, showing excellent efficacy, displayed a Zone of inhibition (ZI) of 15 and 18 mm against E. coli and E. faecalis, respectively, and a minimum inhibitory concentration (MIC) of 62.5 and 31.25 µg/mL against E. coli and E. faecalis, which were comparable to the standard antibiotic Amoxicillin. Furthermore, virtual ADMET analysis was conducted to assess the pharmacokinetic profiles of synthesized compounds. The results suggested that most of the derivatives exhibited favorable bioavailability and drug-like parameters. Spectroscopic investigation revealed that the absorption maxima and optical densities of compounds were influenced by the nature and position of the substituents. Specifically, an electron-withdrawing group at the distant positions enhanced conjugation, leading to red-shifted absorption maxima.