Mitochondria-targeted Re(I) complexes bearing guanidinium as ligands and their anticancer activity
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ORIGINAL PAPER
Mitochondria‑targeted Re(I) complexes bearing guanidinium as ligands and their anticancer activity Shu‑Fen He1,2 · Nan‑Lian Pan1 · Bing‑Bing Chen1 · Jia‑Xin Liao1 · Min‑ying Huang1 · Hai‑Jun Qiu1 · Dong‑Chun Jiang1 · Jun‑Jie Wang1 · Jia‑Xi Chen1 · Jing Sun1 Received: 18 August 2020 / Accepted: 12 October 2020 © Society for Biological Inorganic Chemistry (SBIC) 2020
Abstract As the “powerhouse” of a cell, mitochondria maintain energy homeostasis, synthesize ATP via oxidative phosphorylation, generate ROS signaling molecules, and modulate cell apoptosis. Herein, three Re(I) complexes bearing guanidinium derivatives have been synthesized and characterized. All of these complexes exhibit moderate anticancer activity in HepG2, HeLa, MCF-7, and A549 cancer cells. Mechanism studies indicate that complex 3, [Re(CO)3(L)(Im)](PF6)2, can selectively localize in the mitochondria and induce cancer cell death through mitochondria-associated pathways. In addition, complex 3 can effectively depress the ability of cell migration, cell invasion, and colony formation. Graphic abstract
Keywords Re(I) complex · Cytotoxicity · Mitochondria · Apoptosis Shu-Fen He and Nan-Lian Pan have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00775-020-01827-7) contains supplementary material, which is available to authorized users. Extended author information available on the last page of the article
Introduction Mitochondria, as essential organelles in most eukaryotic cells, are related to many biological activities, such as energy metabolism and regulation of programmed cell death [1–3]. Mitochondria have the ability to control the activation
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JBIC Journal of Biological Inorganic Chemistry
of programmed cell death by regulating the translocation of proapoptotic proteins from the mitochondrial intermediate space to cytosol [4]. Numerous studies have developed mitochondria-targeting anticancer drugs and reported their promising application in chemotherapy and diagnosis of several disorders [5–8]. Over the past decades, researches have placed increasing focus on investigating metal complexes and their anticancer activity. Among these compounds, Re(I) complexes have emerged as promising alternatives [9–17]. Compared to other metal complexes that have entered clinical trials, such as platinum [18], ruthenium [19], and titanium [20], studies on Re(I) complexes have only been recently initiated. As a new class of anticancer drugs, a key advantage of Re(I) complexes is their rich spectroscopic properties. For instance, these complexes exhibit high photo stability, long-lived phosphorescence, which simplifies time-resolved detection, and large Stokes shifts, which minimize the possible self-quenching effect [21]. The emission properties of these complexes can be altered by the addition of different ligands. Furthermore, combining various recognition groups and biological molecules into these complexes is anticipated to resu
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