Optimization of Antiproliferative Properties of Triimine Copper(II) Complexes.

IF 5.3 2区材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY

ACS Applied Nano Materials Pub Date : 2024-11-14 Epub Date: 2024-11-04 DOI:10.1021/acs.jmedchem.4c01806

Katarzyna Choroba, Bartosz Zowiślok, Sławomir Kula, Barbara Machura, Anna M Maroń, Karol Erfurt, Cristiana Marques, Sandra Cordeiro, Pedro V Baptista, Alexandra R Fernandes

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引用次数: 0

Abstract

Cu(II) complexes with 2,2':6',2″-terpyridines (terpy) and 2,6-bis(thiazol-2-yl)pyridines (dtpy) with 1- or 2-naphtyl and methoxy-naphtyl were synthesized to elucidate the impact of the triimine core, naphtyl linking mode, and presence of methoxy groups on the antiproliferative activity of [CuCl₂(Lⁿ)]. Their antiproliferative effect was analyzed in ovarian (A2780) and colorectal (HCT116) carcinomas and colorectal carcinoma resistant to doxorubicin (HCT116-DoxR) cell lines and in normal human fibroblasts. Among all complexes, the 1- and 2-naphtyl substituted terpy Cu(II) complexes (Cu1a and Cu1b) showed the strongest cytotoxicity, namely, in HCT116-DoxR 2Dcells and were also capable of inducing the loss of cell viability in 3D HCT116-DoxR spheroids. Their intracellular localization, capability to increase reactive oxygen species (ROS), and interaction with DNA (nonintercalative mode) trigger oxidative DNA cleavage leading to cell death by apoptosis and autophagy. Cu1a and Cu1b do not show in vivo toxicity in a chicken embryo and can interact with bovine serum albumin (BSA).

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优化三亚胺铜(II)配合物的抗增殖特性。

合成了 2,2':6',2″-terpyridines (terpy) 和 2,6-bis(thiazol-2-yl)pyridines (dtpy) 与 1 或 2-萘基和甲氧基萘基的 Cu(II) 配合物，以阐明三亚甲基核心、萘基连接方式和甲氧基的存在对 [CuCl2(Ln)] 抗增殖活性的影响。研究分析了它们在卵巢癌（A2780）、结直肠癌（HCT116）、对多柔比星耐药的结直肠癌（HCT116-DoxR）细胞系以及正常人成纤维细胞中的抗增殖作用。在所有复合物中，1-萘基和 2-萘基取代的萜铜(II)复合物（Cu1a 和 Cu1b）在 HCT116-DoxR 2D 细胞中显示出最强的细胞毒性，在三维 HCT116-DoxR 球体内也能诱导细胞丧失活力。它们在细胞内的定位、增加活性氧（ROS）的能力以及与 DNA 的相互作用（非交联模式）会引发 DNA 氧化裂解，导致细胞凋亡和自噬。Cu1a 和 Cu1b 对鸡胚胎没有体内毒性，并能与牛血清白蛋白（BSA）相互作用。

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来源期刊

ACS Applied Nano Materials Multiple-

CiteScore

8.30

自引率

3.40%

发文量

1601

期刊介绍： ACS Applied Nano Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics and biology relevant to applications of nanomaterials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important applications of nanomaterials.