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丙氨酸和缬氨酸衍生的两种氨基酸钯(II)配合物的合成、表征、细胞毒性及与 DNA/BSA 的结合。

Synthesis, characterization, cytotoxicity and DNA/BSA binding of two amino acid palladium(II) complexes derived from alanine and valine.

机构信息

Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran.

Nanotechnology and Advanced Materials Department, Materials and Energy Research Center, Karaj, Iran.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2022;41(1):97-122. doi: 10.1080/15257770.2021.2011914. Epub 2021 Dec 9.

Abstract

Two novel palladium(II)-amino acid complexes, [Pd(Ala)]·HO () and [Pd(Val)].HO () (Ala = alanine; Val = valine) were synthesized and characterized through FTIR, UV/Vis, H-NMR spectroscopies, CHN analysis, X-ray crystallography and molar conductivity measurement. Furthermore, cytotoxicity of Pd(II) complexes against human leukemia cancer cell line, MOLT4 showed promising cancer cell death (CC = 0.71 ± 0.046 µM for ; CC = 0.85 ± 0.063 µM for ) that were less than cisplatin (1.59 ± 0.25 µM). Moreover, the interaction of both the complexes with DNA and BSA was studied using UV-Vis absorption and emission spectroscopic techniques that demonstrated the bindings occurred via van der Waals forces and hydrogen bond. Furthermore, the fluorescence titration showed that static quenching mechanism plays predominate role in binding process. All results showed that both complexes have more binding tendency to DNA in compared to BSA that can be a significant achievement for further medical purposes as a potential antitumor candidate. Finally, molecular docking simulation was performed for and complexes with DNA and BSA and demonstrated both complexes bind to the groove of DNA mainly by hydrogen bond and interact with site I of BSA via hydrogen bond as well.

摘要

两种新型的钯(II)-氨基酸配合物,[Pd(Ala)]·HO()和[Pd(Val)].HO()(Ala=丙氨酸;Val=缬氨酸)通过 FTIR、UV/Vis、H-NMR 光谱、CHN 分析、X 射线晶体学和摩尔电导率测量进行了合成和表征。此外,钯(II)配合物对人白血病癌细胞系 MOLT4 的细胞毒性显示出有希望的癌细胞死亡(CC=0.71±0.046µM ;CC=0.85±0.063µM ),低于顺铂(1.59±0.25µM)。此外,使用紫外-可见吸收和荧光光谱技术研究了两种配合物与 DNA 和 BSA 的相互作用,表明结合是通过范德华力和氢键发生的。此外,荧光滴定表明,静态猝灭机制在结合过程中起主导作用。所有结果表明,与 BSA 相比,两种配合物与 DNA 的结合倾向更大,这对于进一步的医学用途作为潜在的抗肿瘤候选物来说是一个重要的成就。最后,进行了分子对接模拟与 DNA 和 BSA 的[Pd(Ala)]·HO()和[Pd(Val)].HO()复合物,表明两种配合物主要通过氢键结合到 DNA 的沟中,并通过氢键与 BSA 的 I 型位点相互作用。

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