Celaya Christian A, Martínez Del Sobral Sinitsyna Carmen, Hernández-Ayala Luis Felipe, Solórzano M, Araiza Daniel G, Reina Miguel
Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km. 107 Carretera Tijuana-Ensenada, Ensenada, B.C., C.P. 22800, México.
Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México, C.P. 04510, Ciudad de México, México.
J Mol Graph Model. 2025 Nov;140:109087. doi: 10.1016/j.jmgm.2025.109087. Epub 2025 May 20.
This research explores the interaction nature and adsorption energies of the anticancer agent procarbazine with C and BN nanocages using Density Functional Theory (DFT), AbInitio 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 BN nanocage shows a stronger interaction compared to the C 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 C and BN nanocages as promising candidates for biomedical applications.
本研究利用密度泛函理论（DFT）、从头算分子动力学模拟（AIMD）和对接研究，探索了抗癌药物丙卡巴肼与C和BN纳米笼的相互作用性质及吸附能。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巴肼形成了良好的相互作用。这些相互作用确保了强大的化学吸引力，同时保持了丙卡巴肼的结构完整性。热力学分析证实，吸附过程在能量上是有利的，并且BN纳米笼与C体系相比表现出更强的相互作用。包括态密度（DOS）和分子静电势（MEP）在内的电子性质评估表明，纳米笼不会对丙卡巴肼的电子性质产生负面影响。此外，HOMO-LUMO分析表明，吸附后药物的稳定性增强且反应性发生变化，同时不影响其抗癌功效。生理温度下的AIMD模拟证实了丙卡巴肼-纳米笼复合物的结构稳定性，未观察到解离现象。此外，还进行了对接研究，以评估各种化合物与一条因其低鸟嘌呤含量（15%）而选择的16BP-DNA链（CACTACAATGTTGCAAT）的相互作用潜力。丙卡巴肼的盲对接显示出稳定的加合物，结合能范围为-4.08至-5.95 kcal/mol。丙卡巴肼和其他配体与鸟嘌呤形成加合物时表现出更高的稳定性，表明这种相互作用在稳定化合物-DNA加合物中起关键作用。这些发现强调了C和BN纳米笼作为生物医学应用有前景候选物的潜力。
