作为CYP3A4潜在基质的Ni2+和Cu2+复合物N-{2,6-二二) -N-梅西形式胺二甲酸盐的结构和功能特性
Segun D Oladipo1,2, Sizwe J Zamisa3, Abosede A Badeji4
1Department of Chemical Sciences, Olabisi Onabanjo University, P.M.B 2002, Ago-Iwoye, Nigeria. segun.oladipo@oouagoiwoye.edu.ng.
Scientific reports
|August 17, 2023
概括
这项研究合成和表征了新的 (Ni2+) 和铜 (Cu2+) 金属复合物. 这些复合物显示出作为CYP3A4抑制剂的前景,可能改善癌症化疗的疗效.
科学领域:
- 协调化学 协调化学
- 生物有机化学 生物有机化学
- 计算化学计算化学
背景情况:
- 由于其多功能性质,金属化合物提供了多样化的应用.
- N'-(2,6-二二) -N-梅西甲基胺二甲基酸盐 (L) 作为金属复合体合成的配体.
- 酶CYP3A4在药物代谢中起着至关重要的作用,并与癌症等疾病有关.
研究的目的:
- 用一种新型的dithiocarbamate连接体合成和表征Ni2+和Cu2+复合体.
- 研究合成复合物的晶体结构和功能性质.
- 评估这些复合物作为CYP3A4抑制剂的药物和生物医学应用的潜力.
主要方法:
- 合成[Ni-(L) 2] (1) 和[Cu-(L) 2 (2) 复合物.
- 使用1H和13C核磁共振 (NMR),元素分析和单晶X射线衍射进行结构性表征.
- 计算模拟包括赫什菲尔德表面分析,分子对接,基于高斯混合模型的聚类和电场分析,以预测结合亲缘关系和酶相互作用.
主要成果:
- 发现这两个复合体是同型的,在金属中心周围有一个扭曲的正方形平面几何.
- 包括键长度,角度和NMR值在内的计算和实验数据显示出很好的一致性.
- 模拟显示了化合物1和2与CYP3A4的显著结合,平均相互作用能量分别为-97和-87kcal/mol,表明潜在的抑制活性.
结论:
- 合成的Ni2+和Cu2+复合体表现出有希望的CYP3A4抑制特性.
- 这种抑制可能会降低癌症中CYP3A4的过度表达,从而提高化疗剂的疗效和持续时间.
- 该研究强调了这些生物金属化合物的潜力,作为基质模仿抑制剂,用于未来的分子金属电子和药物开发研究.
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