Novel anticancer agents, Pt complex with 1-pyrrolidineacetic acid ligand: Synthesis, biological activity, DNA interaction, molecular docking, and dynamic study

IF 5.2 2区化学 Q2 CHEMISTRY, PHYSICAL Journal of Molecular Liquids Pub Date : 2025-04-15 Epub Date: 2025-02-10 DOI:10.1016/j.molliq.2025.127126

Diba Kadivar , Mahboube Eslami Moghadam , Morteza Rezaeisadat

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Abstract

New aliphatic cyclic N-substituted glycine derivative, as asymmetric N, O donate bidentate ligand, and its new Pt complex, [Pt(NH₃)₂(pyrro-gly)]NO₃, where pyrro-gly is 1-Pyrrolidineacetic acid were synthesized and characterized. To investigate the hydrolytic properties, solubility, lipophilicity, and stability of both ligand and Pt complex were analyzed. The cytotoxic properties of both compounds were ascertained on normal and cancerous cell lines in comparison with carboplatin. An apoptosis assay was used to follow the mechanism of cell death in cancerous cells. Regarding isothermal titration, hypochromic absorption was seen during DNA-complex interaction. Fluorescence data illustrated that static quenching occurred. Also, binding constants in EtBr and Hoechst systems showed that groove binding accrues during DNA interaction. Based on circular dichroism studies, electrostatic approaches to DNA and then groove binding interaction were proved which are in agreement with viscosity data. In the docking study, the estimated free binding energy for the Pt complex system is more negative than the ligand system in DNA interaction. The molecular dynamics investigation revealed that the system attained equilibrium after a duration of 100 ns, as determined through the analysis of RMSD, RMSF, and Rg. The findings of the RMSF analysis demonstrated that the majority of residues experienced notable shifts from their starting positions. The computed binding free energy of the complex with DNA was found, which suggested a thermodynamically favorable interaction. The analysis of RDF at equilibrium revealed that Thymine and Guanine residues exhibited the most pronounced and least complex distributions, respectively.

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新型抗癌药物铂- 1-吡咯烷乙酸配合物：合成、生物活性、DNA相互作用、分子对接及动力学研究

合成了一种新的脂肪族环N取代甘氨酸衍生物，作为不对称N， O给体双齿配体，及其新的Pt配合物[Pt(NH3)2（吡咯-gly）]NO3，其中吡咯-gly为1-吡咯烷乙酸。研究了配体和铂配合物的水解性能、溶解度、亲脂性和稳定性。与卡铂比较，确定了这两种化合物在正常和癌细胞系上的细胞毒性。采用细胞凋亡法观察癌细胞的死亡机制。在等温滴定中，dna -络合物相互作用过程中出现了低色吸收。荧光数据表明发生了静态猝灭。此外，EtBr和Hoechst系统的结合常数表明，在DNA相互作用过程中，凹槽结合产生。在圆二色性研究的基础上，证明了DNA的静电方法和凹槽结合相互作用，这与粘度数据一致。在对接研究中，DNA相互作用中Pt复合物系统的估计自由结合能比配体系统更负。分子动力学研究表明，通过RMSD、RMSF和Rg的分析，系统在100 ns后达到平衡。RMSF分析的结果表明，大多数残基从它们的起始位置经历了显著的变化。计算得到了该配合物与DNA的结合自由能，表明其具有良好的热力学相互作用。平衡态RDF分析表明，胸腺嘧啶和鸟嘌呤残基分别表现出最明显和最不复杂的分布。

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来源期刊

Journal of Molecular Liquids 化学-物理：原子、分子和化学物理

CiteScore

10.30

自引率

16.70%

发文量

2597

审稿时长

78 days

期刊介绍： The journal includes papers in the following areas: – Simple organic liquids and mixtures – Ionic liquids – Surfactant solutions (including micelles and vesicles) and liquid interfaces – Colloidal solutions and nanoparticles – Thermotropic and lyotropic liquid crystals – Ferrofluids – Water, aqueous solutions and other hydrogen-bonded liquids – Lubricants, polymer solutions and melts – Molten metals and salts – Phase transitions and critical phenomena in liquids and confined fluids – Self assembly in complex liquids.– Biomolecules in solution The emphasis is on the molecular (or microscopic) understanding of particular liquids or liquid systems, especially concerning structure, dynamics and intermolecular forces. The experimental techniques used may include: – Conventional spectroscopy (mid-IR and far-IR, Raman, NMR, etc.) – Non-linear optics and time resolved spectroscopy (psec, fsec, asec, ISRS, etc.) – Light scattering (Rayleigh, Brillouin, PCS, etc.) – Dielectric relaxation – X-ray and neutron scattering and diffraction. Experimental studies, computer simulations (MD or MC) and analytical theory will be considered for publication; papers just reporting experimental results that do not contribute to the understanding of the fundamentals of molecular and ionic liquids will not be accepted. Only papers of a non-routine nature and advancing the field will be considered for publication.