Drug Discovery & Development Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India.
Drug Discovery & Development Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India; Northwestern University, Feinberg School of Medicine, Department of Neurology, Chicago, IL 60611, USA.
Int J Biol Macromol. 2022 Nov 1;220:415-425. doi: 10.1016/j.ijbiomac.2022.08.106. Epub 2022 Aug 17.
In this study, we have shown the interaction between opium poppy alkaloid noscapine-based ionic liquid [Pip-Nos]OTf and ct-DNA using UV-visible absorption spectroscopy, fluorescence spectroscopy, CD, and computational studies. The absorption spectra showed a hypochromic shift with no shift in the absorption maxima suggesting groove or electrostatic binding. Fluorescence spectra showed an enhancement in fluorescence emission suggesting that the probable mode of binding should be groove binding. Ethidium bromide (EB) competitive and Ionic strength study showed the absence of intercalative and electrostatic modes of interaction. Further, CD analysis of ct-DNA suggested a groove binding mode of interaction of [Pip-Nos]OTf with ct-DNA. [Pip-Nos]OTf displayed a strong binding with the target ct-DNA with a molecular docking score of -41.47 kJ/mol with all 3D coordinates and full conformation. Also, molecular binding contact analyses depicted the stable binding of drug and ct-DNA with potential hydrogen bonds and hydrophobic interactions. The structural superimposition dynamics analysis showed the stable binding of [Pip-Nos]OTf with the ct-DNA model through RMSD statistics. Moreover, the ligand interaction calculations revealed the involvement of large binding energy along with a high static number of molecular forces including the hydrogen bonds and hydrophobic interactions in their complexation. These significant results report the potency of [Pip-Nos]OTf and its important futuristic role in cancer therapeutics.
在这项研究中，我们使用紫外可见吸收光谱、荧光光谱、CD 和计算研究表明，罂粟碱类离子液体[Pip-Nos]OTf 与 ct-DNA 之间存在相互作用。吸收光谱显示出减色效应，而吸收最大值没有移动，表明沟槽或静电结合。荧光光谱显示出荧光发射的增强，表明可能的结合模式应为沟槽结合。溴化乙锭（EB）竞争和离子强度研究表明不存在插入和静电相互作用模式。此外，ct-DNA 的 CD 分析表明[Pip-Nos]OTf 与 ct-DNA 的相互作用是沟槽结合模式。[Pip-Nos]OTf 与靶标 ct-DNA 具有很强的结合能力，分子对接评分为-41.47 kJ/mol，具有所有 3D 坐标和完整构象。此外，分子结合接触分析描绘了药物和 ct-DNA 与潜在氢键和疏水相互作用的稳定结合。结构叠加动力学分析表明，[Pip-Nos]OTf 通过 RMSD 统计与 ct-DNA 模型稳定结合。此外，配体相互作用计算揭示了在其络合过程中涉及大的结合能以及包括氢键和疏水相互作用在内的大量分子力的静态数量。这些重要的结果报告了[Pip-Nos]OTf 的效力及其在癌症治疗中的重要未来作用。
