d-Galactose-conjugated pyrimidine thioureas as potent antimicrobial agents: rapid green synthesis, structure-activity
Nguyen Dinh Thanh1, Vu Ngoc Toan2, Ngo Hong Anh Thu1
1Faculty of Chemistry, University of Science (Vietnam National University, Hanoi) 19 Le Thanh Tong, Cua Nam Ha Noi Viet Nam nguyendinhthanh@hus.edu.vn.
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.
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