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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

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Published on: May 28, 2014

作为潜在的抗癌药物,Pd(II) /二啡/黄素复合物作为潜在的抗癌剂.

Jocely L Dutra^1,2, João Honorato³, Angélica Graminha¹

¹Departamento de Química, Universidade Federal de São Carlos - UFSCar, CP 676, CEP 13561-901, São Carlos, SP, Brazil. jocely.dut@hotmail.com.

Dalton transactions (Cambridge, England : 2003)

|June 28, 2024

概括

此摘要是机器生成的。

新的二复合物与黄素显示出强大的抗癌活性,对抗各种癌症细胞系. 综合体A1表现出显著的细胞毒性,诱导亡和ROS生产在耐思的卵巢癌细胞.

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科学领域:

无机化学无机化学
药用化学医学化学
癌症研究癌症研究

背景情况:

(II) 复合物正在研究它们对癌细胞的选择性体外细胞毒性.
黄素是一种天然产品,具有抗癌性质,并作为金属复合体中的配体进行了探索.
结合 (II) 与素配体和黄素,旨在开发新的抗癌药物.

研究的目的:

合成和表征一系列新的 ((II) - 库尔库 - 啡复合物.
评估这些复合物的体外抗癌活性,对抗各种人类瘤和非瘤细胞系.
为了研究这种最强大的复合物的作用机制,在耐思普拉丁的卵巢癌细胞中.

主要方法:

合成了五个 (II) 复合物:[Pd (cur) (PPh3) 2]PF6 (A1) 到[Pd (cur) (dppf) ]PF6 (A5).
使用元素分析,光谱学 (NMR,UV-Vis,IR) 和X射线晶体学对选定的复合体进行表征.
使用MTT测定对MDA-MB-231,SK-BR-3,A549,MRC-5,A2780和A2780cis细胞系进行体外细胞毒性评估.

主要成果:

所有合成的复合物 (A1-A5) 在体外对测试的瘤细胞系表现出显著的抗癌活性.
复合物通常显示较低的IC50值 (更高的强度) 与自由的黄素和前体相比.
复合物A1表现出优异的细胞毒性,特别是针对MDA-MB-231和卵巢癌细胞系 (A2780,A2780cis),表现优于思.
在A2780cis细胞中复杂的A1诱导的亡和细胞循环停止以及强大的ROS生成.

结论:

合成的 (II) 库尔库明复合物代表了有前途的抗癌药物,其活性比自由库尔库明更强.
综合体A1是进一步研究的有力候选者,特别是在卵巢癌中克服西斯普拉丁耐药性.
该机制涉及ROS诱导,细胞亡和细胞循环停止,突出其治疗潜力.