Host–guest interactions of Crizotinib with natural and modified cyclodextrins: a combined molecular docking and molecular dynamics simulation approaches

IF 1.9 4区化学 Q4 CHEMISTRY, PHYSICAL

Molecular Simulation Pub Date : 2023-09-28 DOI:10.1080/08927022.2023.2259493

Elham Mohebbi, Leila Hokmabady, Fatemeh Ravari

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引用次数: 0

Abstract

ABSTRACTIn this work, molecular docking and molecular dynamics (MD) simulation were applied to investigate the ability of natural cyclodextrins (CDs; Alpha, Beta and Gamma Cyclodextrins) and modified CDs (hydroxypropyl, random methyl and amino Beta Cyclodextrins) to form the stable inclusion complexes (ICs) with Crizotinib, the oral small molecule kinase inhibitor as a chemotropic drug. Results of molecular docking and MD simulation studies demonstrated that Crizotinib forms stable ICs with all natural and modified CDs and in the presence of this drug, all six CDs become more rigid. The presence of Crizotinib and the release of water molecules result in a decrease in the number of hydrogen bonds between cyclodextrins (CDs) and solvent molecules within the encapsulated CDs, compared to the hydrogen bonds observed in free CDs. Additionally, HPBCD exhibited the strongest affinity for binding and established the highest quantity of hydrogen bonds with Crizotinib. Finally, all results of this paper demonstrated the potential of using this formulation to improve the bioavailability of the selected drug.KEYWORDS: Molecular dockingMolecular dynamics simulationNatural cyclodextrinsModified cyclodextrinsCrizotinib Disclosure statementNo potential conflict of interest was reported by the author(s).

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克唑替尼与天然和修饰环糊精的主客体相互作用:结合分子对接和分子动力学模拟方法

摘要:本文采用分子对接和分子动力学(MD)模拟的方法研究了天然环糊精(CDs;α、β和γ环糊精)和修饰的CDs(羟丙基、随机甲基和氨基β环糊精)与口服小分子激酶抑制剂克唑替尼形成稳定的包合物(ICs)。分子对接和MD模拟研究的结果表明，克唑替尼与所有天然和修饰的CDs形成稳定的ic，并且在该药物存在下，所有六种CDs都变得更加刚性。与游离cd中观察到的氢键相比，克唑替尼的存在和水分子的释放导致封装cd内环糊精(cd)和溶剂分子之间的氢键数量减少。此外，HPBCD表现出最强的结合亲和力，并与克唑替尼建立了最多的氢键。最后，本文的所有结果都证明了使用该配方可以提高所选药物的生物利用度。关键词:分子对接分子动力学模拟天然环糊精改性环糊精斯克唑替尼披露声明作者未报告潜在利益冲突。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Simulation 化学-物理：原子、分子和化学物理

CiteScore

3.80

自引率

9.50%

发文量

128

审稿时长

3.1 months

期刊介绍： Molecular Simulation covers all aspects of research related to, or of importance to, molecular modelling and simulation. Molecular Simulation brings together the most significant papers concerned with applications of simulation methods, and original contributions to the development of simulation methodology from biology, biochemistry, chemistry, engineering, materials science, medicine and physics. The aim is to provide a forum in which cross fertilization between application areas, methodologies, disciplines, as well as academic and industrial researchers can take place and new developments can be encouraged. Molecular Simulation is of interest to all researchers using or developing simulation methods based on statistical mechanics/quantum mechanics. This includes molecular dynamics (MD, AIMD), Monte Carlo, ab initio methods related to simulation, multiscale and coarse graining methods.