Green synthesis of pyrrolo[2,3-d]pyrimidine Schiff bases via ionic liquid catalysis: computational and experimental exploration of antimicrobial potentials

Abstract

A green and efficient synthetic approach was developed for a novel series of pyrrolo[2,3-d]pyrimidine-based Schiff bases (PPR1a–d) using microwave-assisted ionic liquid catalysis. The ionic liquid [HMIM][TFSI] served as both catalyst and solvent, enabling solvent-free synthesis at 120 W microwave power and 80 °C within 10 min, yielding products in excellent yields of 87.0–93.0%. All compounds were structurally confirmed by FT-IR, ¹H NMR, ¹³C NMR, ESI-MS, and elemental analysis. Among them, PPR1b exhibited the most potent antimicrobial activity, showing an inhibition zone of 29.0 mm against Bacillus subtilis and 18.5 mm against Candida albicans, outperforming streptomycin (23.5 mm) and fluconazole (15.3 mm), respectively. Cytotoxicity studies using the brine shrimp lethality assay yielded LC₅₀ values of 25.6 μg mL⁻¹ (PPR1b) and 29.3 μg mL⁻¹ (PPR1c), indicating low toxicity. DFT analysis revealed a minimum HOMO–LUMO energy gap of 2.85 eV for PPR1b, while molecular docking showed a binding energy of −9.1 kcal mol⁻¹ with S. aureus DNA gyrase. ADMET and 100 ns MD simulations confirmed drug-likeness, GI absorption, BBB permeability, and complex stability. This study uniquely integrates green synthesis, in vitro antimicrobial validation, and in silico insights, offering promising antimicrobial agents with sustainable production routes.