Breast Cancer Stem Cell Active Copper(II) Complexes with Naphthol Schiff Base and Polypyridyl Ligands
Breast Cancer Stem Cell Active Copper(II) Complexes with Naphthol Schiff Base and Polypyridyl Ligands
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DOI：
10.3390/inorganics9010005
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发表时间：
2021-01-01
期刊：
影响因子：
2.9
通讯作者：
Suntharalingam, Kogularamanan
中科院分区：
文献类型：
--
作者：
Northcote-Smith, Joshua;Johnson, Alice;Suntharalingam, Kogularamanan
乳腺癌干细胞（CSCs）是肿瘤细胞的一个亚群，可促进乳腺癌复发和转移。目前的治疗方法无法完全去除乳腺CSCs，因此开发新的化疗药物以临床相容的剂量去除乳腺CSCs至关重要。本文介绍了铜（II）配合物[Cu(L-2)（1,10-菲罗啉）]PF6(2)和[Cu(L-3)（1,10-菲罗啉）]PF6(3)的合成、表征和抗乳腺CSC性能，它们由三齿（O，N，S）配位萘酚席夫碱配体(L-2 = （E)-1-（（2-（甲基硫）乙基）亚氨基）甲基）萘-2-醇或L-3 = (E)-1-（（（2-（乙基硫）乙基）亚氨基）甲基）萘-2-醇和1,10-菲罗啉组成。铜（II）配合物（2和3）在微摩尔范围内杀死单层和三维系统中培养的乳腺CSCs。值得注意的是，2和3对乳腺CSC乳房微球的作用比盐碱霉素更有效（高达4.5倍），盐碱霉素是一种已建立的抗乳腺CSC药物。此外，基于细胞的研究表明，2和3很容易被乳腺CSCs吸收，并在短时间（0.5-1小时）暴露后提高细胞内活性氧（ROS）水平。后者可能是2和3诱导乳腺CSC死亡的潜在机制。
Breast cancer stem cells (CSCs) are a sub-population of tumour cells that can promote breast cancer relapse and metastasis. Current treatments are unable to completely remove breast CSCs, therefore it is essential to develop new chemotherapeutics that can remove breast CSCs at clinically compatible doses. Here we present the synthesis, characterisation, and anti-breast CSC properties of copper(II) complexes, [Cu(L-2)(1,10-phenanthroline)]PF6 (2) and [Cu(L-3)(1,10-phenanthroline)]PF6 (3) comprising of a tridentate (O,N,S) coordinated naphthol Schiff base ligand (L-2 = (E)-1-(((2-(methylthio)ethyl)imino)methyl)naphthalen-2-ol or L-3 = (E)-1-(((2-(ethylthio)ethyl)imino)methyl)naphthalen-2-ol and 1,10-phenanthroline. The copper(II) complexes (2 and 3) kill breast CSCs, cultured in monolayer and three-dimensional systems, in the micromolar range. Notably, 2 and 3 are more potent towards breast CSC mammospheres than salinomycin (up to 4.5-fold), an established anti-breast CSC agent. Further, cell-based studies indicate that 2 and 3 are readily taken up by breast CSCs and elevate intracellular reactive oxygen species (ROS) levels upon short exposure times (0.5-1 h). The latter is likely to be the underlying mechanism by which 2 and 3 induces breast CSC death.