作为微管不稳定剂的Indolo[2,3-e]benzazocines和Indolo[2,3-f]benzazonines及其铜 (II) 复合物
Christopher Wittmann1, Orsolya Dömötör2, Irina Kuznetcova1
1Institute of Inorganic Chemistry, University of Vienna, Währinger Strasse 42, A-1090 Vienna, Austria. vladimir.arion@univie.ac.at.
Dalton transactions (Cambridge, England : 2003)
|July 11, 2023
概括
新的indolo[2,3-e]benzazocine和indolo[2,3-f]benzazonine铜 (II) 复合物表现出强大的抗增殖活性. 这些化合物选择性地向癌细胞,通过抑制结素结合部位的结素组合.
科学领域:
- 药用化学 医学化学
- 无机化学 无机化学
- 化学生物学 化学生物学
背景情况:
- 印度洛[2,3-e]扎素和印度洛[2,3-f]扎素是具有潜在生物活性的异环基架.
- 铜 (II) 复合物因其多样化的应用,包括抗癌性质而受到探索.
研究的目的:
- 合成和描述新型的Indolo[2,3-e]benzazocine和Indolo[2,3-f]benzazonine连接体及其铜 (II) 复合体.
- 评估这些合成化合物对各种癌症细胞系的抗增殖活性和作用机制.
主要方法:
- 使用NMR,ESI-MS,SC-XRD和燃烧分析进行合成和表征.
- 确定包括pKa,稳定常数和可溶性在内的物理化学性质.
- 在体外抗增殖试验,乙基化物排位研究,管分解实验和分子建模.
主要成果:
- 成功合成并对六个配体 (HL1-HL6) 和它们的铜 (II) 复合体 (1-6) 进行了完整的表征.
- 化合物表现出显著的抗增殖活性,在低微分子到亚微分子范围内的IC50值,对Colo320,Colo205和MCF-7细胞系具有显著的抗增殖活性.
- 对几种化合物观察到针对恶性细胞系的选择性活性,DNA被确定不是主要的标;结核素组合抑制被证实是机制,HL1和复合物1与菌素部位结合.
结论:
- 合成的indolo[2,3-e]benzazocine和indolo[2,3-f]benzazonine铜 (II) 复合物代表了一类有前途的抗癌药物.
- 这些化合物通过抑制氨酸组合来发挥它们的抗增殖作用,向菌素结合部位.
- 复合物1是第一个据报道的过渡金属复合物,能够有效地与氨酸-氨酸口袋结合,突出显示其作为新型治疗的潜力.
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