合成,细胞毒性和生物大分子结合:三种异构体的酸复合物与双酸生物活性分子作为辅配体
Hehe Bai1, Wenjun Gong1, Yating Pang1
1Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Institute of Molecular Science, Shanxi University, Taiyuan 030006, China.
International journal of biological macromolecules
|May 28, 2023
概括
三种新的酸复合物显示出作为金属基药物的潜力,其中一种异构体诱导癌细胞亡和细胞循环停止. 人体血清白蛋白可以作为这些复合物的输送系统.
科学领域:
- 协调化学 协调化学
- 药用化学 医学化学
- 生物物理化学 生物物理化学
背景情况:
- 酸复合物因其治疗潜力而受到探索.
- 生物活跃的小分子,如8-基因和pyrazinamide可以作为co-ligands.
- 了解结构-活性关系对于药物设计至关重要.
研究的目的:
- 合成和表征与8-基和pyrazinamide的同位素基复合物.
- 评估这些复合物的细胞毒性和生物活性.
- 研究复合体与DNA和人血清白蛋白 (HSA) 的结合相互作用.
主要方法:
- 合成和X射线衍射用于结晶结构的确定.
- 在HeLa细胞上进行细胞毒性测试 (IC50).
- 光光谱法以确定结合常数与小牛胸腺DNA (CT-DNA) 和HSA.
- 对HSA复杂引证的结构分析.
主要成果:
- 合成了三种异构体复合物[RuNO(Qn) ((PZA) Cl],并进行了结构特征.
- 复合体对HeLa细胞表现出显著的细胞毒性 (IC50:0.77-1.45μM).
- 复杂的P2诱导的亡和G1细胞周期停止.
- 结合性研究揭示了CT-DNA和HSA的相互作用,HSA作为潜在的纳米传递系统.
- 结构阐明表明P2通过非协调性键结合HSA子域I.
结论:
- 异构体结构显著影响酸复合物的生物活性.
- P2复合体显示出有前途的抗癌性质.
- 可以将HSA作为这些金属基药物候选物的载体.
- 这项工作为设计新的基于金属的治疗方法提供了基础.
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