合成,晶体结构,细胞毒性,详细的实验和计算CT-DNA相互作用研究的2-picolinate复合物Pd(II) 和Pt(II) 的综合体
Nasimeh Jamgohari1, Hassan Mansouri-Torshizi1, Effat Dehghanian1
1Department of Chemistry, University of Sistan and Baluchestan, Zahedan, Iran.
Journal of biomolecular structure & dynamics
|August 24, 2023
概括
新的 (II) 和 (II) 复合物显示出对癌细胞有前途的细胞毒性活性. 这些金属复合物表现出与DNA的选择性相互作用,表明它们有可能作为具有改善脂性质的新型抗癌剂.
科学领域:
- 无机化学 无机化学 有机化学
- 药用化学 医学化学
- 生物化学 生物化学
背景情况:
- 开发新的基于金属的抗癌药物至关重要.
- (Platinum) 复合物,如卡博普拉丁,是已知的化疗药物.
- 探索 (II) 复合体提供了替代治疗策略.
研究的目的:
- 合成和表征新的 (II) 和 (II) 复合物与乙烯基二胺和2 - 皮里丁碳酸盐.
- 评估这些复合体对癌症和正常细胞系的体外细胞毒性活性.
- 研究这些复杂物与CT-DNA的相互作用机制.
主要方法:
- 改进的合成产生>80%的纯度.
- 使用FT-IR,UV-Vis,NMR,导电性和元素分析进行表征.
- 在体外细胞毒性测试 (IC50测定),DNA结合研究 (UV-Vis,光,粘度,凝电泳),分割系数,对接和分子动力学模拟.
主要成果:
- 合成了高产量的[Pd(en) ((2-pyc) ]+和[Pt(en) ((2-pyc) ]+复合物.
- 结构分析证实了Pt (II) 综合体的正方形平面几何.
- 复合体对HCT-116和MCF-7细胞系表现出选择性细胞毒性,其中碳烯 > 2-pyc > Pt(II) > Pd(II).
- 化合物通过沟结合机制表现出DNA结合,涉及H键和范德瓦尔斯力.
- 与西斯丁相比,观察到更高的脂友性.
结论:
- 合成的Pd (II) 和Pt (II) 复合体在体外表现出显著和选择性的抗癌活性.
- 这些复合物通过沟结合与CT-DNA相互作用,这与实验和计算发现一致.
- 这些发现支持这些新型金属复合物的潜力,作为开发新抗癌疗法的化合物.
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