Synthesis, anticancer activity and mechanism of action of Fe(III) complexes

IF 3.5 4区医学 Q2 CHEMISTRY, MEDICINAL

Drug Development Research Pub Date : 2024-09-27 DOI:10.1002/ddr.22264

Xiaoqian Zhao, Ying Qian, Shanshan Hu, Yingbiao Tian

引用次数: 0

Abstract

To inhibit the growth and metastasis of triple-negative breast cancer (TNBC), two Fe(III) thiosemicarbazone complexes (Fe1 and Fe2) were designed and synthesized. The structures of the Fe(III) complexes were characterized by single crystal X-ray diffraction. The antiproliferative activity of Fe1 and Fe2 against four cancer lines (MDA-MB-231, T98G, HepG2, 143B) and human renal proximal tubular epithelial cell line (HK-2) was evaluated by MTT assay. Among all cells, Fe2 showed significant cytotoxicity to TNBC cells (MDA-MB-231), with an IC₅₀ value of 12.38 μM. Furthermore, Fe2 showed less toxicity to HK-2 cells. The two Fe(III) complexes can produce excess of reactive oxygen species, decrease of mitochondrial membrane potential, and induce DNA damage, then lead to apoptosis of MDA-MB-231 cells. In addition, Fe1 and Fe2 can also inhibit migration and invasion of MDA-MB-231 cells. This study provides guidance for the development of metal complexes that inhibit the growth and metastasis of TNBC.

查看原文本刊更多论文

Fe(III)配合物的合成、抗癌活性和作用机制

为了抑制三阴性乳腺癌（TNBC）的生长和转移，我们设计并合成了两种硫代氨基甲酸铁（III）配合物（Fe1 和 Fe2）。单晶 X 射线衍射表征了 Fe(III) 复合物的结构。通过 MTT 试验评估了 Fe1 和 Fe2 对四种癌症细胞株（MDA-MB-231、T98G、HepG2、143B）和人类肾近曲小管上皮细胞株（HK-2）的抗增殖活性。在所有细胞中，Fe2 对 TNBC 细胞（MDA-MB-231）具有显著的细胞毒性，IC50 值为 12.38 μM。此外，Fe2 对 HK-2 细胞的毒性较小。这两种铁(III)复合物能产生过量的活性氧，降低线粒体膜电位，诱导DNA损伤，进而导致MDA-MB-231细胞凋亡。此外，Fe1 和 Fe2 还能抑制 MDA-MB-231 细胞的迁移和侵袭。这项研究为开发抑制 TNBC 生长和转移的金属复合物提供了指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Drug Development Research 医学-药学

CiteScore

6.40

自引率

2.60%

发文量

104

审稿时长

6-12 weeks

期刊介绍： Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.