Adsorption of procarbazine anticancer drug over C24 and B12N12 nanocages: A comparative DFT study

IF 2.7 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling Pub Date : 2025-05-20 DOI:10.1016/j.jmgm.2025.109087

Christian A. Celaya , Carmen Martínez del Sobral Sinitsyna , Luis Felipe Hernández-Ayala , M. Solórzano , Daniel G. Araiza , Miguel Reina

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引用次数: 0

Abstract

This research explores the interaction nature and adsorption energies of the anticancer agent procarbazine with C₂₄ and B₁₂N₁₂ nanocages using Density Functional Theory (DFT), Ab Initio Molecular Dynamics simulations (AIMD), and docking studies. Both nanocages exhibited excellent structural stability and formed favorable interactions with procarbazine through chemisorption phenomena. These interactions ensure robust chemical attraction while preserving the structural integrity of the procarbazine. Thermodynamic analyses confirmed that the adsorption process is energetically favorable, and that B₁₂N₁₂ nanocage shows a stronger interaction compared to the C₂₄ system. Electronic property evaluations, including Density of States (DOS) and Molecular Electrostatic Potential (MEP), indicated that the nanocages do not negatively impact the electronic properties of procarbazine. Furthermore, HOMO-LUMO analyses revealed enhanced stability and change in the reactivity for the drug upon adsorption without compromising its anticancer efficacy. AIMD simulations at physiological temperature confirmed the structural stability of the procarbazine-nanocage complexes, with no dissociation observed. Additionally, the docking studies were conducted to evaluate the interaction potential of various compounds with a 16BP-DNA strand (CACTACAATGTTGCAAT) selected for its low guanine content (15 %). Blind docking of procarbazine revealed stable adducts with binding energies ranging from −4.08 to −5.95 kcal/mol. Procarbazine and other ligands demonstrated greater stability when forming adducts with guanine, suggesting that this interaction plays a critical role in stabilizing compound-DNA adducts. These findings underscore the potential of C₂₄ and B₁₂N₁₂ nanocages as promising candidates for biomedical applications.

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异丙卡嗪抗癌药物在C24和B12N12纳米笼上的吸附：比较DFT研究

本研究利用密度泛函理论（DFT）、Ab Initio分子动力学模拟（AIMD）和对接研究等方法，探讨了抗癌药物procarbazine与C24和B12N12纳米笼的相互作用性质和吸附能。两种纳米笼均表现出优异的结构稳定性，并通过化学吸附现象与丙卡嗪形成良好的相互作用。这些相互作用确保了强大的化学吸引力，同时保持了丙卡嗪的结构完整性。热力学分析证实了吸附过程在能量上是有利的，与C24体系相比，B12N12纳米笼表现出更强的相互作用。电子性能评价，包括态密度（DOS）和分子静电势（MEP），表明纳米笼对丙卡嗪的电子性能没有负面影响。此外，HOMO-LUMO分析显示，在不影响其抗癌功效的情况下，吸附后药物的稳定性和反应性发生了变化。在生理温度下的AIMD模拟证实了丙卡嗪-纳米笼配合物的结构稳定性，没有观察到解离。此外，对接研究评估了各种化合物与16bp dna链（CACTACAATGTTGCAAT）的相互作用潜力，该链因其鸟嘌呤含量低（15%）而被选中。对丙卡嗪进行盲对接，得到了结合能在- 4.08 ~ - 5.95 kcal/mol之间的稳定加合物。丙卡嗪和其他配体在与鸟嘌呤形成加合物时表现出更大的稳定性，这表明这种相互作用在稳定化合物- dna加合物中起着关键作用。这些发现强调了C24和B12N12纳米笼作为生物医学应用的有希望的候选物的潜力。

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来源期刊

Journal of molecular graphics & modelling 生物-计算机：跨学科应用

CiteScore

5.50

自引率

6.90%

发文量

216

审稿时长

35 days

期刊介绍： The Journal of Molecular Graphics and Modelling is devoted to the publication of papers on the uses of computers in theoretical investigations of molecular structure, function, interaction, and design. The scope of the journal includes all aspects of molecular modeling and computational chemistry, including, for instance, the study of molecular shape and properties, molecular simulations, protein and polymer engineering, drug design, materials design, structure-activity and structure-property relationships, database mining, and compound library design. As a primary research journal, JMGM seeks to bring new knowledge to the attention of our readers. As such, submissions to the journal need to not only report results, but must draw conclusions and explore implications of the work presented. Authors are strongly encouraged to bear this in mind when preparing manuscripts. Routine applications of standard modelling approaches, providing only very limited new scientific insight, will not meet our criteria for publication. Reproducibility of reported calculations is an important issue. Wherever possible, we urge authors to enhance their papers with Supplementary Data, for example, in QSAR studies machine-readable versions of molecular datasets or in the development of new force-field parameters versions of the topology and force field parameter files. Routine applications of existing methods that do not lead to genuinely new insight will not be considered.