Synthesis of bioactive 1,4-disubstituted 1,2,3-triazole-linked Thiosemicarbazone derivatives using Cu2O microbeads catalysis for enhanced antibacterial and antioxidant activities

Abstract

This study focuses on the design, synthesis and evaluation of antibacterial and antioxidant properties of 1,4-disubstituted 1,2,3-triazole-linked thiosemicarbazone derivatives.The synthesis involved a multistep process, beginning with the preparation of alkyne derivatives from three benzaldehyde derivatives (4-hydroxybenzaldehyde, vanillin, and salicylaldehyde) and using flower-like Cu₂O microbeads as a catalyst. The synthesized compounds were evaluated for antibacterial activity against four bacterial strains: Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Bacillus subtilis (B. subtilis), and Staphylococcus aureus (S. aureus), at concentrations ranging from 10 to 80 mg/mL, using ciprofloxacin (CIP) as a reference. Among the derivatives, Compound 3c, (Z)-2-(4-((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)-3-methoxybenzylidene)hydrazine-1-carbothioamide,exhibited the most potent antibacterial activity against E. coli, with a zone of inhibition of 22±0.1 mm at 80 mg/mL. Compound 3a, (Z)-2-(4-((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)benzylidene)hydrazine-1-carbothioamide, showed the highest efficacy against B. subtilis, with an inhibition zone of 21±0.4 mm. Antioxidant assays, including DPPH and ABTS, revealed Compound 3c to have the lowest IC50 values (2 ± 0.4 μg/mL and 160±0.1 μg/mL, respectively), indicating strong antioxidant activity. These results demonstrate that Cu₂O-catalyzed synthesis and chemical substitution in 1,4-disubstituted 1,2,3-triazole-linked thiosemicarbazone derivatives significantly enhance their antibacterial and antioxidant activities, making them promising candidates for therapeutic development.