通过化疗信息学和分子动力学模拟研究吉西他滨和 5-氟尿嘧啶对乳腺癌的协同作用

IF 2.3 3区 化学 Q3 CHEMISTRY, PHYSICAL International Journal of Quantum Chemistry Pub Date : 2024-10-14 DOI:10.1002/qua.27498
Sureba Sukumaran, Azar Zochedh, Kaliraj Chandran, Asath Bahadur Sultan, Thandavarayan Kathiresan
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引用次数: 0

摘要

同时靶向不同的蛋白质机制,可以减少对人体的伤害并提高生物活性。吉西他滨和 5-氟尿嘧啶(GE5F)加合物能共同摧毁癌细胞,提高抗击乳腺癌的疗效。本研究利用基集 B3LYP/6-311 G 改进了 GE5F 加合物的结构。自然键分析显示了 GE5F 加合物的分子间相互作用。电子跃迁为 π → π*,并对紫外至可见光谱进行了理论计算。利用 HOMO 和 LUMO 之间的能隙来研究 GE5F 加合物的结构稳定性和反应活性;计算得出的能隙 (ΔE) 为 3.912 eV。对 Mulliken 电荷群进行了评估,并确定了复合结构的静电位。利用 RDG 分析评估了 GE5F 的弱相互作用,并利用 LOL 和 ELF 分析研究了拓扑方面的问题。对 GE5F 加合物的吸附、分布、代谢、排泄和毒性特性进行了研究,结果证实 GE5F 加合物属于药物相似分子,符合安全参数。利用乳腺癌靶蛋白进行了分子对接实验。从对接得分来看,复合物分子具有更高的结合亲和力,这验证了吉西他滨和 5-氟尿嘧啶之间更好的组合相互作用。复合物分子与 PARP 蛋白的结合力最强,为-9.4 kcal/mol,通过分子动态模拟 100 ns,观察到四个氢键相互作用,复合物分子的结合力得到了稳定的证实。这些硅学发现将为体外和体内实验铺平道路,从而更好地提高 FDA 批准药物的疗效。
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Combinatory Effect of Gemcitabine and 5-Fluorouracil Investigated Through Chemoinformatics and Molecular Dynamics Simulation Against Breast Cancer

Co-delivering FDA-approved drugs can be less harmful and boost biological activity by targeting different protein mechanism at same time. Gemcitabine and 5-Fluorouracil (GE5F) adduct work together to destroy cancer cells and increase the efficacy in the fight against breast cancer. The basis set B3LYP/6-311 G was utilized in this investigation to improve the structure of GE5F adduct. The natural bond analysis exhibited the intermolecular interactions of the GE5F adduct. Electronic transitions were seen to be π → π*, and theoretical calculations were performed for the ultraviolet to visible spectrum. The energy gap between HOMO and LUMO was used to study the GE5F adduct's structural stability and reactivity; the computed energy gap (ΔE) was 3.912 eV. The Mulliken charge population was assessed and the complex structure's electrostatic potential was established. Weak interactions of the GE5F were assessed using RDG analysis, and topological aspects were investigated using LOL and ELF analysis. Investigating the GE5F adduct's adsorption, distribution, metabolism, excretion, and toxicity properties, the results confirmed that GE5F adduct comes under the safety parameters being a drug-likeness molecule. Molecular docking experiments were conducted using target proteins for breast cancer. The complex molecule had a higher binding affinity as indicated by the docking scores, which validated the better combinatorial interaction between gemcitabine and 5-Fluorouracil. With − 9.4 kcal/mol, the complex molecule's strongest binding capacity was against PARP protein, and stable confirmation was observed through molecular dynamic simulation for 100 ns with four hydrogen bond interactions. These in silico finding will pave a way for in vitro and in vivo experiments with better enhancement of FDA approved drugs.

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来源期刊
International Journal of Quantum Chemistry
International Journal of Quantum Chemistry 化学-数学跨学科应用
CiteScore
4.70
自引率
4.50%
发文量
185
审稿时长
2 months
期刊介绍: Since its first formulation quantum chemistry has provided the conceptual and terminological framework necessary to understand atoms, molecules and the condensed matter. Over the past decades synergistic advances in the methodological developments, software and hardware have transformed quantum chemistry in a truly interdisciplinary science that has expanded beyond its traditional core of molecular sciences to fields as diverse as chemistry and catalysis, biophysics, nanotechnology and material science.
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