What question did this study set out to answer?

This study aims to evaluate the antimicrobial and antioxidant potential of novel coumarin-based hybrids.

May 29, 2026Open Access

In silico DFT, ADMET and molecular docking studies of novel coumarin-linked pyrazole and quinoline derivatives as antimicrobial and antioxidant agents

Key Points

This study aims to evaluate the antimicrobial and antioxidant potential of novel coumarin-based hybrids.
Synthesize and characterize ten coumarin derivatives via multistep reactions with solvent optimization in DMF:Ethanol (1:1).
Perform antimicrobial evaluation against bacterial and fungal strains using MIC determinations.
Conduct molecular docking against target proteins and evaluate DFT calculations for electronic properties.
Compound 7a exhibits the highest antimicrobial potency with an MIC of 25 μg/mL against bacterial strains.
Compound 7a shows excellent antioxidant activity with an IC50 of 20.23 ± 0.29 mg/mL, comparable to ascorbic acid.
Molecular docking reveals compound 7b has the highest docking score of -9.71186 kcal/mol, indicating strong theoretical binding affinity.

Abstract

Abstract Ten novel coumarin-based hybrids comprising coumarin–pyrazole ( 7a–e ) and coumarin–quinoline ( 11a–e ) derivatives were synthesized via multistep reactions and characterized spectroscopically. Solvent optimization identified DMF: Ethanol (1:1) with H 2 SO 4 as optimal conditions, achieving 88% yield in 2–3 h. Antimicrobial evaluation against four bacterial strains ( Bacillus subtilis , Staphylococcus aureus , Escherichia coli , Acinetobacter baumannii ) and one fungal strain ( Aspergillus niger ) revealed compound 7a as the most potent (MIC: 25 μg/mL), superior to standard drugs. Antioxidant screening showed that 7a exhibited excellent activity (IC 50 : 20.23 ± 0.29 mg/mL), comparable to that of ascorbic acid. Molecular docking against three target proteins (4WMZ, 5FNR, 4LOL) demonstrated strong binding affinity, with 7b showing the highest docking score (− 9.71186 kcal/mol) against 4WMZ. Notably, compound 7b showed the highest predicted binding affinity in silico, whereas compound 7a demonstrated the superior experimental antimicrobial activity; this discrepancy underscores that docking scores offer predictive, not confirmatory, evidence of biological potency. DFT calculations (B3LYP/6–311++ G(d,p)) elucidated electronic properties, including HOMO–LUMO gap (3.8640 eV), Mulliken charge distribution, RDG, ELF, LOL, thermodynamic parameters, and global reactivity descriptors. In silico ADMET profiling revealed favorable physicochemical and drug-like properties for most derivatives; however, uniformly high predicted genotoxicity scores (> 0.99) and moderate hERG cardiotoxicity liability were identified, highlighting the need for rigorous experimental safety validation prior to further development. This integrated approach establishes coumarin–pyrazole and coumarin–quinoline hybrids as promising multifunctional therapeutic agents with antimicrobial and antioxidant potential.

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