Abstract：
Cancer is a global public health problem characterized by deviations in the mechanisms that control cell proliferation, resulting in mutations and variations in the structure of DNA. The mechanisms of action of chemotherapeutic drugs are related to their interactions and binding with DNA; consequently, the development of antineoplastic agents that target DNA has extensively focused on use of acridine, a heterocyclic molecule that binds to deoxyribonucleic acid via intercalation, a process that modifies DNA and makes replication impossible. In this context, this study aimed to computationally investigate how acridine intercalators interact with DNA by evaluating the mechanism of interactions, binding, and interaction energies using quantum mechanics calculations. Molecular electrostatic potential (MEP) analysis revealed that acridine has well- distributed negative charges in the center of the molecule, indicative of a dominant electron-rich region. Acridine exhibits well-defined π orbitals (HOMO and LUMO) on the aromatic rings, suggesting that charge transfer occurs within the molecule and may be responsible for the pharmacological activity of the compound. Structural analysis revealed that acridine interacts with DNA mainly through hydrogen bonds between HAcridine… ODNA with bond lengths ranging from 2.370 Å to 3.472 Å. The Binding energy (ΔEBind) showed that acridine interacts with DNA effectively for all complexes and the electronic energy results (E+ZPE) for complexes revealed that the complexes are more stable when the DNA-centered acridine molecule. The Laplacian-analysis topological QTAIM parameter (∇2ρ(r)) and total energy (H(r)) categorized the interactions as being non-covalent in nature. The RGD peak distribution in the NCI analysis reveals the presence of van der Waals interactions, predominantly between the intercalator and DNA. Accordingly, we confirm that acridine/DNA interactions are relevant for understanding how the intercalator acts within nucleic acids.
摘要：
癌症是一个全球性的公共卫生问题，其特征是控制细胞增殖的机制存在偏差。导致DNA结构的突变和变异。化疗药物的作用机制与它们与DNA的相互作用和结合有关；因此，靶向DNA的抗肿瘤剂的开发广泛集中在吖啶的使用上，通过嵌入与脱氧核糖核酸结合的杂环分子，一个改变DNA并使复制变得不可能的过程。在这种情况下，这项研究旨在通过评估相互作用的机制来计算研究吖啶嵌入剂如何与DNA相互作用，绑定,和相互作用能使用量子力学计算。分子静电势（MEP）分析显示，吖啶在分子中心具有均匀分布的负电荷，指示主要的富电子区域。吖啶在芳香环上表现出明确的π轨道（HOMO和LUMO），这表明电荷转移发生在分子内，可能是化合物药理活性的原因。结构分析显示，吖啶与DNA相互作用主要通过Hacridine之间的氢键...ODNA，键长范围为2.370µ至3.472µ。结合能（ΔEBind）表明，吖啶与所有复合物的DNA有效相互作用，复合物的电子能结果（EZPE）表明，当DNA中心的吖啶分子时，复合物更稳定。拉普拉斯分析拓扑QTAIM参数（2ρ（r））和总能量（H（r））将相互作用分类为本质上是非共价的。NCI分析中的RGD峰分布揭示了范德华相互作用的存在，主要在嵌入剂和DNA之间。因此，我们确认吖啶/DNA相互作用与理解嵌入剂在核酸中的作用是相关的。
