Abstract

Cyclometalated iridium(III) complexes represent a promising approach to developing new anticancer metallodrugs. In this work, three phosphorescent cyclometalated iridium(III) complexes Ir1–Ir3 have been explored as mitochondria-targeted anticancer agents. All three complexes display higher antiproliferative activity than cisplatin against the cancer cells screened, and with the IC₅₀ values ranging from 0.23 to 5.6 μM. Colocalization studies showed that these complexes are mainly localized in the mitochondria. Mechanism studies show that these complexes exert their anticancer efficacy through initiating a series of events related to mitochondrial dysfunction, including depolarization of mitochondrial membrane potential (MMP), elevation of intracellular reactive oxygen species (ROS) levels, and induction of apoptosis.

Graphic abstract

Mitochondria-targted cyclometalated iridium complexes induce apoptosis through depolarized mitochondria, elevation of intracellular ROS and activated caspase.

中文翻译：

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线粒体靶向的磷光环金属铱（III）配合物：合成，表征和抗癌特性。

摘要

环金属化铱（III）配合物是开发新的抗癌金属药物的有前途的方法。在这项工作中，已经探索了三种磷光环金属化铱（Ir1–Ir3）络合物作为针对线粒体的抗癌剂。与IC ₅₀相比，这三种复合物均具有比顺铂更高的抗增殖活性。值范围从0.23至5.6μM。共定位研究表明，这些复合体主要位于线粒体中。机理研究表明，这些复合物通过引发一系列与线粒体功能障碍相关的事件发挥其抗癌作用，包括线粒体膜电位（MMP）的去极化，细胞内活性氧（ROS）水平的升高以及细胞凋亡的诱导。

图形摘要

线粒体阻滞的环金属化铱配合物通过去极化的线粒体，细胞内ROS升高和活化的胱天蛋白酶诱导细胞凋亡。