In recent years salinomycin has emerged as a promising anticancer drug. Many literature reports have proved its remarkable antiproliferative activity. Moreover, chemical modifications of salinomycin lead to analogues with even higher cytotoxicity against cancer cell lines and a better selectivity index for malignant cells than those of the unmodified compound or a standard anticancer drug such as doxorubicin. In this paper we report the synthesis of a series of twelve novel salinomycin conjugates and their characterization by spectroscopic and spectrometric methods. Salinomycin was conjugated with different triphenylphosphonium cations in order to find out whether the conjugation with mitochondrial targeting vectors would have a beneficial impact on biological properties. Salinomycin and its novel conjugates were tested to determine their in vitro antiproliferative and antimicrobial activity. Taking into account the presence of triphenylphosphonium moiety, the impact of the obtained analogues on mitochondria activity was evaluated by MitoTrackers dyes, furthermore their apoptosis effect and cell cycle arrest were assessed. In addition, the changes in the mitochondrial membrane potential were measured and the ability to generate reactive oxygen species was assessed. Finally, we conducted biophysical studies to investigate the impact of the obtained salinomycin analogues on mitochondrial respiration rates and their electrophysiological properties. Results of this study have proved that conjugation of salinomycin with phosphonium cations leads to promising results in the search for promising anticancer agents.

中文翻译：

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盐霉素季鏻盐的抗癌活性


近年来，沙利霉素已成为一种很有前途的抗癌药物。许多文献报道证明了其显著的抗增殖活性。此外，盐霉素的化学修饰导致类似物对癌细胞系具有更高的细胞毒性，并且对恶性细胞的选择性指数优于未修饰的化合物或标准抗癌药物如阿霉素。在本文中，我们报道了一系列 12 种新型盐霉素偶联物的合成及其通过光谱和光谱方法表征它们。将盐霉素与不同的三苯基鏻阳离子偶联，以找出与线粒体靶向载体的偶联是否会对生物学特性产生有益影响。对 Salinomycin 及其新型偶联物进行测试，以确定其体外抗增殖和抗菌活性。考虑到三苯基膦部分的存在，通过 MitoTrackers 染料评估所获得的类似物对线粒体活性的影响，进而评估它们的凋亡效应和细胞周期停滞。此外，还测量了线粒体膜电位的变化，并评估了产生活性氧的能力。最后，我们进行了生物物理学研究，以研究获得的盐霉素类似物对线粒体呼吸速率及其电生理特性的影响。这项研究的结果证明，盐霉素与鏻阳离子的结合在寻找有前途的抗癌剂方面取得了有希望的结果。