铁中的NSAID衍生的tris(pyrazolyl) 甲联体的抗癌潜力在铁中的三明治复合物中
Alberto Gobbo1, Sarah A P Pereira2,3, Fátima A R Mota2
1University of Pisa, Department of Chemistry and Industrial Chemistry, Via G. Moruzzi 13, I-56124 Pisa, Italy. fabio.marchetti@unipi.it.
Dalton transactions (Cambridge, England : 2003)
|July 29, 2024
概括
新的铁复合物与三 (pyrazolyl) 甲配体显示出抗增殖活性. 癌细胞中的细胞毒性与生物活性碎片有关,而不是与DNA结合或ROS产生.
科学领域:
- 协调化学 协调化学
- 药用化学 医学化学
- 生物化学 生化学
背景情况:
- 三 () 甲 (tpm) 和其衍生物是协调化学中的多功能联体.
- 铁复合物被探索为其潜在的治疗应用.
- 将像布洛芬这样的生物活性碎片纳入连接体可以创建新的金属药物.
研究的目的:
- 合成和表征新型铁 (II) 复合物与三 (pyrazolyl) 甲基连接物,包括以布洛芬和flurbiprofen结合的化衍生物.
- 评估这些配体及其相应的铁复合体对各种癌症和非癌症细胞系的抗增殖活性.
- 研究作用机制,重点关注酶抑制 (COX-2,HNE) 和DNA结合和活性氧物种 (ROS) 生产的潜在作用.
主要方法:
- 三聚醇甲 (tpm),2,2,2-三聚醇乙醇 (tpmOH),tpmIBU和tpmFLU连接物的合成.
- 铁 (II) 复合物的形成和特征 [Fe (tpm) X (sup) 2 (sub) ]Cl (sub) 2 (sub) (1-4) 使用IR和多核NMR光谱学.
- 单晶X射线衍射用于tpmIBU连接体结构的确定.
- 评估水性介质中的复杂行为 (可溶性,分离系数,稳定性).
- 在A2780,A2780cis,A549,HEK 293T和BJ细胞系的体外抗增殖试验.
- 对COX-2和HNE的酶抑制试验.
- 评估ROS生产和DNA结合能力.
主要成果:
- 成功合成了包含tpm,tpmOH,tpmIBU和tpmFLU连接体的新型铁 (II) 复合体.
- 复合物3和4 (来自tpmIBU和tpmFLU) 显示出针对癌细胞系的显著抗增殖活性.
- 复合体3和4的细胞毒性主要归因于内置的布洛和弗鲁比的部分.
- 在观察到的细胞毒性中,没有观察到DNA结合或增强ROS生产的显著作用.
- 复合物在水和生理条件下显示出不同的溶解度和稳定性.
结论:
- 合成的铁 (II) 复合物,特别是那些含有雌性化NSAID片段的复合物,表现出有希望的抗增殖作用.
- 这些复合物的作用机制似乎依赖于连接体,主要由生物活性基团介导.
- 对这些金属药物的进一步研究可能会导致新的癌症治疗方法的开发.
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