d-Galactose-conjugated pyrimidine thioureas as potent antimicrobial agents: rapid green synthesis, structure–activity relationships and molecular modelling

Abstract

A series of D-galactose-conjugated pyrimidine-based thioureas 8a–l was efficiently synthesized using an environmentally benign ionic liquid–microwave protocol. Optimal conditions employing [BMIM][BF₄] under microwave irradiation (100 W) afforded excellent yields (up to 96%) within 60 s, with the ionic liquid showing good recyclability. The synthesized compounds were evaluated for antibacterial and antifungal activities against a broad panel of pathogenic microorganisms. Several derivatives exhibited potent antimicrobial effects, with MIC values comparable to or superior to reference drugs. Structure–activity relationship analysis revealed that ortho-hydroxyl substitution and synergistic hydroxyl/methoxy patterns significantly enhanced biological activity. Among the series, compound 8l (2-OH-4-OMe) emerged as the most potent and broad-spectrum candidate. In silico ADMET analysis suggested favourable drug-like characteristics for non-oral antimicrobial applications. Molecular docking studies supported the experimental results, demonstrating strong and stable binding of compound 8l within bacterial and fungal enzyme active sites. Overall, these findings highlight D-galactose-conjugated pyrimidine thioureas as promising antimicrobial scaffolds.