基于乙化单糖功能化协配体的强抗癌Pt(II) 复合物:合成特征和生物分析
Na Wang1, Ning Yuan2, Zhimin Lv1
1Inner Mongolia University, Research Center for Glycochemistry of Characteristic Medicinal Resources, Department of Chemistry and Chemical Engineering, Hohhot, People's Republic of China.
Journal of inorganic biochemistry
|September 4, 2025
概括
新型 (II) 复合物与糖改性联体具有强烈的抗癌活性,特别针对对抗性癌细胞. 这些复合物向GLUT1, 提供了一个有前途的新治疗策略, 对正常细胞的毒性降低.
科学领域:
- 有机金属化学
- 医学化学
- 癌症生物学
背景情况:
- (II) 复合物是已知的抗癌药物.
- 开发新的 (II) 复合物对于克服耐药性和改善治疗指数至关重要.
- 基胺配体为设计 (II) 复合物提供了多功能支架.
研究的目的:
- 合成和表征包含单糖功能化联体的新型Pt(II) 复合物.
- 评估这些复合物的体外抗癌功效与各种人类癌细胞系,包括耐思的细胞系.
- 阐明作用机制,包括GLUT1依赖和亡途径.
主要方法:
- 通过两步反应合成Pt(II) 复合物 (C1-C12),其中包括银(I) 四甲酸和乙化β-d-葡萄糖合.
- 使用胃癌 (MKN 45),结肠癌 (RPMI 4788) 和肺癌 (A549) 细胞系进行体外抗癌活性评估.
- 在耐思的A549/DDP细胞和正常的胃 (GES) 和结肠 (NCM 460) 表皮细胞中进行评估.
- GLUT1抑制剂 (quercetin) 研究,细胞形态分析 (明亮场,Hoechst 33342染色),流细胞测量和西部斑点分析 (PARP,caspase 3,BCL-2).
主要成果:
- 复合物C9和C12在体外显示出显著的抗癌作用.
- 这些复合物在耐思肺癌细胞中表现出较高的疗效,在正常细胞中表现出较低的毒性.
- 在C9和C12中观察到GLUT1依赖的抗癌活性,而不是对照的oxaliplatin.
- 通过PARP,酶3和BCL-2途径诱导细胞亡.
结论:
- 具有糖改性联体的新型Pt(II) 复合物显示出有前途的抗癌性质,特别是对抗耐药性癌症类型.
- 观察到的GLUT1依赖机制表明癌症治疗的向方法.
- 这些发现突显了这些复合物的潜力,作为下一代基于的抗癌药物,具有更好的安全性.
相关概念视频
00:43Complexometric Titration: Ligands
1.1K
Different monodentate and polydentate ligands are used as complexing agents in complexometric titration reactions. The formation of complexes by mono- and bidentate ligands involves two or more intermediate steps, limiting their use as complexing agents. In comparison, polydentate ligands can form complexes with metal ions in a single-step process, facilitating sharper end points. This means polydentate ligands, such as amino carboxylic acid derivatives, are most commonly employed in...
1.1K
01:22EDTA: Chemistry and Properties
2.2K
Polydentate ligands are most widely used in complexometric titrations because they form more stable complexes with the metal ions than mono- or bidentate ligands due to the chelate effect. Examples of polydentate ligands are ethylenediaminetetraacetic acid (EDTA), crown ethers, and cryptands. The most important feature of optimal polydentate ligands is the ability to form 1:1 complexes in a single-step process. Amino carboxylic acid derivatives are frequently used as complexing agents. EDTA is...
2.2K
02:52Stereoisomerism
12.4K
Isomerism in Complexes
Isomers are different chemical species that have the same chemical formula.
Transition metal complexes often exist as geometric isomers, in which the same atoms are connected through the same types of bonds but with differences in their orientation in space. Coordination complexes with two different ligands in the cis and trans positions from a ligand of interest form isomers. For example, the octahedral [Co(NH3)4Cl2]+ ion has two isomers (Figure 1) In the cis...
Isomers are different chemical species that have the same chemical formula.
Transition metal complexes often exist as geometric isomers, in which the same atoms are connected through the same types of bonds but with differences in their orientation in space. Coordination complexes with two different ligands in the cis and trans positions from a ligand of interest form isomers. For example, the octahedral [Co(NH3)4Cl2]+ ion has two isomers (Figure 1) In the cis...
12.4K