Neurobehavioral Pharmacology Laboratory, Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Department of Molecular Medicine, School of Interdisciplinary Science and Technology, Jamia Hamdard, New Delhi 110062, India.
Biophys Chem. 2022 Jun;285:106808. doi: 10.1016/j.bpc.2022.106808. Epub 2022 Mar 23.
The mechanisms of interaction of DNA with pharmacological molecules are critical to understanding their therapeutic actions on physiological systems. Piperlongumine is widely studied for its anticancer potential. Multi-spectrometry, calorimetry and in silico studies were employed to study the interaction of piperlongumine and calf thymus DNA. UV-Vis spectroscopy illustrated a hyperchromic pattern in spectra of the calf thymus DNA-piperlongumine complex, while fluorescent quenching was observed in emission spectral studies. Competitive displacement assay demonstrated higher displacement and binding constant for DNA-rhodamine B complex by piperlongumine than DNA-methylene blue complex. Differential scanning calorimetry presented non-significant changes in melting temperature and molecular docking presented the precise interaction site of piperlongumine with calf thymus DNA at minor groove. Further, piperlongumine treatment did not result in pBluescript KS plasmid DNA cleavage as revealed from the DNA topology assay. All these experiments confirmed the binding of piperlongumine with DNA through minor groove binding mode.
DNA 与药理分子相互作用的机制对于理解它们对生理系统的治疗作用至关重要。胡椒碱因其抗癌潜力而受到广泛研究。采用多光谱法、量热法和计算机模拟研究了胡椒碱与小牛胸腺 DNA 的相互作用。紫外可见光谱表明小牛胸腺 DNA-胡椒碱复合物的光谱呈现增色模式，而荧光猝灭实验则观察到发射光谱的变化。竞争置换实验表明，胡椒碱与 DNA-若丹明 B 复合物的置换和结合常数均高于 DNA-亚甲蓝复合物。差示扫描量热法显示熔点无显著变化，分子对接则呈现出胡椒碱与小牛胸腺 DNA 之间在小沟处的精确相互作用位点。此外，DNA 拓扑结构测定实验表明，胡椒碱处理不会导致 pBluescript KS 质粒 DNA 断裂。所有这些实验都证实了胡椒碱通过小沟结合模式与 DNA 的结合。
