From In Silico Design to Bioactivity: Synthesis and Pharmacological Profiling of 3-Substituted Quinazoline-2,4-dione Heterocycles

A series of novel 3-substituted quinazoline-2,4(1H,3H)-dione derivatives was designed, synthesized, and evaluated for their anticonvulsant, antibacterial, and antifungal activities. Anticonvulsant efficacy was assessed in vivo using the maximal electroshock (MES) seizure model, while antibacterial and antifungal activities were screened against selected Gram-positive, Gram-negative bacterial, and fungal strains. To support the experimental findings and elucidate possible binding interactions, molecular docking studies were carried out against relevant biological targets for antibacterial (PDB ID: 6BPP), antifungal (PDB ID: 7VPR), and anticonvulsant activity (PDB ID: 2Z5X). Among the synthesized compounds, compound 4h exhibited significant anticonvulsant activity by effectively inhibiting extensor seizures in the MES model at a dose of 30 mg/kg, showing comparable efficacy to the reference drug phenytoin sodium. Compound 4f demonstrated broad-spectrum antibacterial activity against Gram-positive bacteria ( Bacillus subtilis , Staphylococcus aureus ) and Gram-negative bacteria ( Escherichia coli , Pseudomonas aeruginosa ), inhibiting microbial growth at 100 µg/mL. Additionally, compound 4b displayed potent antifungal activity against Candida albicans and Aspergillus niger at 100 µg/mL, surpassing the activity of the standard antifungal agent griseofulvin. The study highlights the quinazoline-2,4-dione heterocyclic scaffold as a promising pharmacophore for the development of multifunctional bioactive agents with potential therapeutic relevance and reduced adverse effects. The combined in silico and experimental findings provide a valuable foundation for further structural optimization and pharmacological exploration.