Synthesis and antimicrobial properties of 2-[(7-ethyl-3-methylxanthin-8-yl)sulfanyl]acetohydrazide derivatives

Antimicrobial resistance (AMR) represents a major global health threat, driving the urgent search for new therapeutic agents. Hybrid molecules based on xanthine and 1,2,4-triazole scaffolds present a promising direction due to their potential multi-target antimicrobial activities. This study aimed at synthesizing new 2-[(7-ethyl-3-methylxanthin-8-yl)sulfanyl]acetohydrazide derivatives containing 1,2,4-triazole moieties, characterizing their structures, and evaluating their antimicrobial and antifungal properties. A series of previously undescribed compounds was synthesized using N-substituted isothiocyanates and further S-alkylation/cyclization strategies. The structures were confirmed via 1H NMR spectroscopy, elemental analysis; mass spectrometry was additionally used for representative derivative 14. Antimicrobial activity was assessed against E. coli, S. aureus, P. aeruginosa and C. albicans by broth dilution methods to determine minimum inhibitory and bactericidal/fungicidal concentrations. All synthesized derivatives were structurally characterized with high confidence. Most compounds exhibited weak to moderate antibacterial and antifungal activity. Notably, the amide and nitrile derivatives displayed moderate antifungal activity against C. albicans (MIC 25 μg/mL), comparable to that of ketoconazole (MIC 25 μg/mL). Structure-activity analysis indicated that S-substitution and side-chain modifications improve antimicrobial potency. New xanthine-triazole hybrid molecules were synthesized and characterized, showing that selected derivatives possess promising antimicrobial and antifungal properties. These findings support further optimization and biological exploration of such hybrids as candidates to combat antimicrobial resistance.