Çelik Esra, Meletli Furkan, Özdemir Mücahit, Köksoy Baybars, Danış Özkan, Yalçın Bahattin
Marmara University, Department of Chemistry, 34722 Istanbul, Turkiye.
Bursa Technical University, Department of Chemistry, 16310 Bursa, Turkiye.
Bioorg Chem. 2024 Dec;153:107857. doi: 10.1016/j.bioorg.2024.107857. Epub 2024 Oct 1.
Coumarin and coumarin-thiosemicarbazone hybrids were synthesized and characterized by various techniques such as FT-IR, H NMR, C NMR, MALDI-TOF-MS spectroscopy, and single crystal X-Ray diffractometer (XRD). The photochemical and photophysical properties of the compounds, such as solvatochromism, solubility, and chemical reactivity, were analyzed using UV-vis spectroscopy in different solvents. Due to the potential biological activities of the synthesized compounds, their binding affinity and mechanisms with calf thymus DNA (ct-DNA) and bovine hemoglobin (BHb) were determined using several useful spectrophotometric and theoretical approaches such as UV-vis absorption and fluorescence spectroscopy, molecular docking, and density functional theory (DFT). The experimental results showed that the compounds exhibited strong binding interactions with DNA and BHb. Additionally, the compounds demonstrated predominantly binding modes, such as intercalation and groove binding with DNA and π-π stacking interactions with BHb.To better understand the thermodynamics of these interactions, quenching constants, binding constants, and Gibbs free energy changes (ΔG°) were calculated. Molecular docking and DFT results supported the experimental data regarding the binding affinity and mechanisms of the compounds to DNA and BHb. Overall, this comprehensive study on coumarin and coumarin-thiosemicarbazone hybrids provides valuable insights into their interaction mechanisms with critical biomolecules, highlighting their potential in therapeutic applications as multifunctional agents.
合成了香豆素和香豆素 - 硫代氨基脲杂化物，并通过傅里叶变换红外光谱（FT - IR）、氢核磁共振（¹H NMR）、碳核磁共振（¹³C NMR）、基质辅助激光解吸电离飞行时间质谱（MALDI - TOF - MS）光谱以及单晶X射线衍射仪（XRD）等多种技术对其进行了表征。使用紫外可见光谱在不同溶剂中分析了这些化合物的光化学和光物理性质，如溶剂化显色、溶解度和化学反应性。由于合成化合物具有潜在的生物活性，因此使用紫外可见吸收光谱和荧光光谱、分子对接以及密度泛函理论（DFT）等几种有用的分光光度法和理论方法，测定了它们与小牛胸腺DNA（ct - DNA）和牛血红蛋白（BHb）的结合亲和力及其机制。实验结果表明，这些化合物与DNA和BHb表现出强烈的结合相互作用。此外，这些化合物主要表现出结合模式，如与DNA的嵌入和沟槽结合以及与BHb的π - π堆积相互作用。为了更好地理解这些相互作用的热力学，计算了猝灭常数、结合常数和吉布斯自由能变化（ΔG°）。分子对接和DFT结果支持了关于化合物与DNA和BHb的结合亲和力及其机制的实验数据。总体而言，这项关于香豆素和香豆素 - 硫代氨基脲杂化物的综合研究为它们与关键生物分子的相互作用机制提供了有价值的见解，突出了它们作为多功能药物在治疗应用中的潜力。
