Sulfide-linked 3,4,5-trimethoxyphenyl-thiosemicarbazide/triazole hybrids: Synthesis, antioxidant, antiglycation, DNA cleavage and DNA molecular docking studies

Abstract

Fourteen sulfide-linked 3,4,5-trimethoxyphenyl-thiosemicarbazide/triazole hybrid derivatives containing a variety of structural modifications on the thiosemicarbazide moiety were synthesized. Structure-activity correlations were investigated to determine the influence of structural variations on the antioxidant, antiglycation and DNA cleavage activities. Antioxidant activity was determined using the DPPH radical scavenging and CUPRAC assays. The majority of the derivatives displayed moderate to weak DPPH radical scavenging activity (IC50 = 20.96 to 106.7 μM) compared to ascorbic acid (IC50 = 13.72 μM), with derivatives having π-donating substituents being the most effective. A similar trend was observed for the CUPRAC assay. All derivatives containing electron-donating substituents were more effective than Trolox at reducing copper(II) ion, with Trolox Equivalent Antioxidant Capacity (TEAC) values ranging from 1.44 to 2.45. However, only the nitro derivative was found to be a promising antiglycation agent, inhibiting the formation of advanced glycation end products (AGEs) by 75 % compared to 27 % for the aminoguanidine control. In addition, the majority of the derivatives cleaved pBR322 plasmid DNA in the presence of copper(II) acetate. The interaction of the derivatives with DNA was confirmed by molecular docking studies, which revealed that all of the derivatives bind favorably in the minor groove of DNA.

Keywords

• Trimethoxyphenyl-thiosemicarbazide hybrids
• Antioxidant
• Antiglycation
• DNA cleavage
• DNA molecular docking