Synthesis of Ether and Thioether Derivatives Containing a 1,2,4-Triazole Ring: Antioxidant Activity and Antimicrobial Properties

Abstract

Introduction.The 1,2,4-triazole ring's structural adaptability and wide range of documented biological activities make it a significant heterocyclic scaffold in medicinal chemistry. Objectives. This study synthesized a series of 1,2,4-triazole ether and thioether derivatives (designated A5–A11) from diclofenac and assessed their antimicrobial and antioxidant properties. Materials and Methods.  Diclofenac sodium was converted to diclofenac acid and its methyl ester in the synthetic sequence. This was followed by a reaction with semicarbazide or thiosemicarbazide, cyclization to the corresponding 1,2,4-triazole derivatives, and then alkylation with allyl bromide, benzyl chloride, or isopentyl bromide. FTIR, ¹H-NMR, and ¹³C-NMR spectroscopy were used to characterize the synthesized compounds.The DPPH radical-scavenging assay was used to measure antioxidant activity at 6.25–100 µg/mL. Results.Compound A11 had the lowest reported IC₅₀ value (46.1 µg/mL), followed by A5 (68.32 µg/mL) and A9 (2039 µg/mL). Antimicrobial screening revealed compound-dependent activity against Bacillus cereus, Candida albicans, Staphylococcus aureus, Proteus mirabilis, and Escherichia coli. The largest inhibition zones were produced by A5 against B. cereus (37 mm), A9 against P. mirabilis (27 mm), and A10 against S. aureus (30 mm). Conclusions.The findings show significant differences in biological activity between the synthesized derivatives and offer initial structure-activity data for additional research on 1,2,4-triazole ether and thioether derivatives.