Sulfide-linked 3,4,5-trimethoxyphenyl-thiosemicarbazide/triazole hybrids: Synthesis, antioxidant, antiglycation, DNA cleavage and DNA molecular docking studies
Sulfide-linked 3,4,5-trimethoxyphenyl-thiosemicarbazide/triazole hybrids: Synthesis, antioxidant, antiglycation, DNA cleavage and DNA molecular docking studies
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DOI：
10.1016/j.rechem.2023.100806
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发表时间：
2023-01-31
影响因子：
2.3
通讯作者：
Henry, Geneive E.
中科院分区：
文献类型：
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作者：
Bollinger, Ashton;Brandt, Olivia N.;Henry, Geneive E.
合成了14个硫化物连接的3,4,5-三甲氧基苯基硫代氨基脲/三唑杂化衍生物，其中硫代氨基脲部分含有多种结构修饰。研究了结构-活性相关性，以确定结构变化对抗氧化、抗糖化和DNA切割活性的影响。采用DPPH自由基清除和CUPRAC测定抗氧化活性。与抗坏血酸（IC50 = 13.72 μ M）相比，大多数衍生物具有中等至弱的DPPH自由基清除活性（IC50 = 20.96 ~ 106.7 μ M），其中具有供价取代基的衍生物效果最好。在CUPRAC试验中也观察到类似的趋势。含供电子取代基的衍生物对铜（II）离子的还原效果均优于Trolox，其当量抗氧化能力（TEAC）在1.44 ~ 2.45之间。然而，只有硝基衍生物被发现是一种有前景的抗糖基化剂，抑制晚期糖基化终产物（AGEs）的形成75%，而氨基胍对照为27%。此外，大多数衍生物在乙酸铜（II）存在的情况下裂解pBR322质粒DNA。分子对接研究证实了这些衍生物与DNA的相互作用，发现所有衍生物都在DNA的小凹槽中良好结合。
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 mu M) compared to ascorbic acid (IC50 = 13.72 mu M), with derivatives having pi-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.