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铂(II)配合物的生物物理研究及抗癌行为的简要研究:它们与 DNA/BSA 的结合、分子对接和细胞毒性性质。

Brief Research on the Biophysical Study and Anticancer Behavior of Pt(II) Complexes: Their DNA/BSA Binding, Molecular Docking, and Cytotoxic Property.

机构信息

Department of Chemistry, National Institute of Technology Durgapur, M. G. Avenue, Durgapur713209, WB, India.

Department of Chemistry, Vidyasagar University, Midnapore721102, WB, India.

出版信息

Langmuir. 2022 Nov 8;38(44):13613-13625. doi: 10.1021/acs.langmuir.2c02490. Epub 2022 Oct 27.

Abstract

The potent bidentate carrier ligand 2-picolylamine (pic) has been used to synthesize Pt(II) complexes to know their bioactivity and anticancer property as reflected by PASS prediction software. The dichloro Pt(II) complex [Pt(pic)Cl], , and its hydrolyzed diaqua complex [Pt(pic)(OH)], , were synthesized. The thiol-containing Pt(II) complexes [Pt(pic)(l-cys)], , and [Pt(pic)(L-ac-l-cy)], , were synthesized from , which was obtained from hydrolysis of . Their biomolecular interactions with BSA and DNA were executed by spectroscopic methods, and their cytototoxic property was tested by the MTT assay. In vitro biomolecular interactions of Pt(II) complexes with BSA and DNA were investigated by different spectroscopic and viscosity measurement methods for their pharmacokinetic and pharmacodynamic importance. The conformational change of BSA in the presence of a drug candidate was studied by Förster resonance energy transfer calculation and synchronous and three-dimensional fluorescence spectroscopic studies. A theoretical approach on optimization structures, highest occupied molecular orbital-lowest unoccupied molecular orbital energy, global reactivity parameters, time-dependent density functional theory, and molecular docking with BSA and DNA was executed to strengthen and support the experimental observations. In vitro cytotoxic profiles of the complexes like the anticancer activity and their level of reactive oxygen species production were brought under consideration on A549 cancer cells and the normal human embryonic kidney cell line HEK-293. The cytotoxic property was compared with that of the recognized anticancer drug cisplatin.

摘要

强双齿载体配体 2-吡啶甲胺(pic)已被用于合成 Pt(II)配合物,以了解它们的生物活性和抗癌特性,这反映在 PASS 预测软件中。合成了二氯 Pt(II)配合物[Pt(pic)Cl], 和其水解的二水合配合物[Pt(pic)(OH)], 。从,合成了含硫 Pt(II)配合物[Pt(pic)(l-cys)], 和[Pt(pic)(L-ac-l-cy)], ,是由水解得到的。通过光谱方法研究了它们与 BSA 和 DNA 的生物分子相互作用,并通过 MTT 测定法测试了它们的细胞毒性。通过不同的光谱和粘度测量方法研究了 Pt(II)配合物与 BSA 和 DNA 的体外生物分子相互作用,以了解其药代动力学和药效学的重要性。通过荧光共振能量转移计算和同步和三维荧光光谱研究研究了药物候选物存在下 BSA 的构象变化。对优化结构、最高占据分子轨道-最低未占据分子轨道能量、全局反应性参数、时间相关密度泛函理论和与 BSA 和 DNA 的分子对接进行了理论研究,以加强和支持实验观察。考虑了配合物的体外细胞毒性谱,如抗癌活性和其活性氧产生水平,针对 A549 癌细胞和正常人类胚胎肾细胞系 HEK-293。将细胞毒性与公认的抗癌药物顺铂进行了比较。

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