综合量子化学计算、预测性毒性评估、吸收、分布、代谢、排泄和毒性分析以及分子对接分析,揭示非氧化钒(IV)和有机锡(IV)复合物靶向乳腺癌细胞的治疗潜力

IF 2.3 3区 化学 Q3 CHEMISTRY, PHYSICAL International Journal of Quantum Chemistry Pub Date : 2024-06-24 DOI:10.1002/qua.27438
Maridula Thakur, Shalima Kumari, Sachin Kumar, Meena Kumari
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引用次数: 0

摘要

本研究采用密度泛函理论(DFT)对我们课题组之前制备和报道的邻苯基苯酚基非氧钒(IV)和有机锡(IV)配合物进行了理论计算。本研究利用密度泛函理论量子化学计算探讨了配合物的结构和光谱特性。通过分子对接研究揭示了复合物对所选乳腺癌细胞蛋白 5NWH 和 3HB5 的抑制性质。使用优化的 DFT/B3LYP/6-311++G (d, p) 水平对复合物 1-6 进行了优化并确定了其稳定性。此外,还对分子静电位面进行了模拟计算,以分析非氧化钒(IV)和有机锡(IV)配合物的反应行为。利用 HOMO-LUMO 能量、能隙、化学势 (μ)、电负性 (χ)、硬度 (η) 和软度 (S) 值计算了分子的稳定性和分子反应性。通过分子对接、ADMET 特性和毒性评估进行的硅学分析评估了其抗癌活性、药物相似性和毒性。通过分子对接评估发现,钒络合物 5 的结合常数值很高,为-10.1 kcal mol-1,络合物的抑制常数低至 0.0378 μMol。为验证分子对接研究,还进行了均方根偏差(RMSD)验证,发现复合物的均方根偏差低于 2.0 Å,表明配体与蛋白质复合物的对接程序取得了成功。根据《全球统一制度》(GHS)对这些复合物的毒性行为进行了致命剂量评估,发现它们的化学安全性属于第三类和第五类,因此可以用作未来的金属基药物。
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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Integrated quantum chemical calculations, predictive toxicity assessment, absorption, distribution, metabolism, excretion and toxicity profiling and molecular docking analysis to unveil the therapeutic potential of non-oxovanadium(IV) and organotin(IV) complexes targeting breast cancer cells

In this work, theoretical calculations of o-phenylphenol-based non-oxovanadium(IV) and organotin(IV) complexes, previously prepared and reported by our group, have been carried out by density functional theory (DFT). Density functional theory quantum chemical computations were used to explore the structural and spectroscopic characteristics of the complexes in this study. The inhibitory nature of complexes were revealed via molecular docking research, which were performed against selected breast cancer cell proteins, 5NWH and 3HB5. The optimization and stability of complexes 1–6, were conducted using optimized DFT/B3LYP/6–311++G (d, p) level. Simulated computations of the molecular electrostatic potential surface were also performed to analyze the reactive behavior of the non-oxovanadium(IV) and organotin(IV) complexes. The stability and molecular reactivity of the molecules were computed using the HOMO-LUMO energies, energy gap, chemical potential (μ), electronegativity (χ), hardness (η), and softness (S) values. In silico analysis through molecular docking, ADMET properties and toxicity evaluation was used to assess its anticancer activity, drug-likeness property and toxicity. The binding constant value, evaluated from molecular docking, was found to be very promising, 10.1 kcal mol−1 observed for vanadium complex 5 and the complexes were found to exhibit inhibition constant as low as 0.0378 μMol. Root-mean-square deviation (RMSD) has been carried out to validate molecular docking studies, which have been found to be below 2.0 Å for the complexes, indicating successful docking of the ligand-protein complex by the program. The complexes, evaluated for their toxicity behavior in terms of Lethal Dose, based on Globally Harmonized System (GHS), have been found to be chemical safe falling under the category III and V and hence can find use as future metallo-based 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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