Design, synthesis, and biological evaluation of novel coumarine-1,2,3-triazole hybrids as dual DNA gyrase/superoxide dismutase inhibitors: molecular docking, DFT, and ADMET investigations

A series of eight novel coumarin-1,2,3-triazole hybrid derivatives (6a-h) were synthesized and evaluated for their antimicrobial and antioxidant potentials through in vitro and in silico approaches. Molecular docking studies against DNA gyrase subunit B (PDB ID: 7P2M) revealed that compounds 6b and 6h exhibited superior-binding affinities with docking scores of −5.448 and −5.106 kcal/mol, respectively, surpassing ciprofloxacin (−4.992 kcal/mol). Against superoxide dismutase [Cu-Zn] (PDB ID: 1PU0), compound 6h showed the highest binding affinity (−4.157 kcal/mol), comparable to ascorbic acid (−3.787 kcal/mol). Antimicrobial screening demonstrated that compound 6b displayed potent broad-spectrum activity with MIC values of 50–100 µg/mL against E. coli, P. aeruginosa, S. aureus, and S. pyogenes. Antioxidant evaluation using the DPPH assay showed compound 6g exhibited the highest activity (IC50 = 54.89 ± 1.2 µg/mL), approaching ascorbic acid (52.66 ± 0.8 µg/mL). DFT calculations for compound 6b revealed favorable electronic properties with a HOMO-LUMO energy gap of 3.445 eV and an electrophilicity index of 5.8303 eV. ADMET profiling using SwissADME, ADMETlab 3.0, and ProTox 3.0 demonstrated acceptable drug-likeness parameters, favorable absorption characteristics, and low toxicity profiles. These coumarine-1,2,3-triazole hybrids represent moderate-potency antibacterial and antioxidant scaffolds warranting further structural optimization.