Department of Chemistry, Kurukshetra University, Kurukshetra, 136119 Haryana, India; Council of Scientific and Industrial Research-National Institute of Science Communication and Policy Research, New Delhi 110012, India.
Department of Chemistry, Kurukshetra University, Kurukshetra, 136119 Haryana, India.
Bioorg Chem. 2023 Jul;136:106524. doi: 10.1016/j.bioorg.2023.106524. Epub 2023 Apr 7.
A series of twenty novel (E)-arylidene-hydrazinyl-thiazole derivatives has been synthesized employing α-bromo-β-diketones, thiosemicarbazide, and aromatic/heteroaromatic aldehydes with a simple and facile one-pot multicomponent reaction passageway. This organic transformation proceeds efficiently in aqueous media and demonstrated a large functional group tolerance. The structures and stereochemistry of the regioisomeric product were rigorously characterized using heteronuclear 2D NMR experiments. The binding potential of the synthesized analogs with B-DNA dodecamer d(CGCGAATTCGCG) was primarily screened using molecular modeling tools and further, mechanistic investigations (either groove or intercalation) were performed using various spectroscopic techniques such as UV-Visible, Fluorescence, and Circular dichroism. The absorption spectra showed a hyperchromic shift in the absorption maxima of ctDNA with successive addition of thiazole derivatives, implying groove binding mode of interactions, further supported by displacement assay and circular dichroism analysis. Furthermore, steady-state fluorescence analysis revealed the static mode of quenching and moderate bindings between the ligand and DNA biomolecule. The competitive studies showed that the derivatives having a pyridinyl (heteroaromatic) group in their structure, bind with the nucleic acid of calf-thymus (ctDNA) more effectively in the minor groove region as compared with the aromatic substitutions.
已经采用α-溴代-β-二酮、缩氨基硫脲和芳族/杂芳族醛，通过简单易行的一锅多组分反应途径合成了一系列二十种新型（E）-芳亚甲基-腙基-噻唑衍生物。这种有机转化在水介质中高效进行，并表现出对大功能基团的高容忍性。利用异核二维 NMR 实验严格表征了区域异构体产物的结构和立体化学。使用分子建模工具对合成类似物与 B-DNA 十二聚体 d(CGCGAATTCGCG) 的结合潜力进行了初步筛选，并进一步使用各种光谱技术（如紫外可见、荧光和圆二色性）进行了机制研究（沟槽或嵌入）。吸收光谱显示，随着噻唑衍生物的连续加入，ctDNA 的吸收最大值发生了增色位移，表明存在沟槽结合模式的相互作用，进一步得到置换实验和圆二色性分析的支持。此外，稳态荧光分析表明，配体与 DNA 生物分子之间存在静态猝灭模式和中等结合。竞争研究表明，与芳基取代物相比，其结构中具有吡啶基（杂芳基）基团的衍生物更有效地结合小牛胸腺（ctDNA）的核酸，在小沟区域。
