Guan Yingzhen, Nguyen Michel, Robert Anne, Liu Yan, Meunier Bernard
School of Chemical Engineering and Light Industry, Higher Education Mega Center, Guangdong University of Technology (GDUT) Guangzhou 510006 P. R. China
Laboratoire de Chimie de Coordination du CNRS 205 Route de Narbonne 31077 Toulouse Cedex 4 France
RSC Med Chem. 2024 Jun 4;15(9):3048-3056. doi: 10.1039/d4md00171k. eCollection 2024 Sep 19.
Cancer cell proliferation and metastasis are known to be dependent on angiogenesis which is regulated by several parameters including copper availability. Tetradentate monoquinoline (TDMQ) ligands constitute a series of chelators tailored to regulate copper homeostasis due to their specificity for copper(ii) with respect to Cu(i) or other biometals like iron or zinc. One of these chelators, TDMQ20 efficiently inhibits both proliferation and migration of several human cancer cell lines, better than the reference drug 5-fluorouracil, and with higher selectivity indexes with respect to non-cancer human cells. The biological activity of TDMQ20 may be driven by the coordination chemistry of copper, and the ability of this chelator to restore copper homeostasis and its subsequent redox properties. The anticancer mechanism of action of TDMQ20 involves intracellular production of reactive oxygen species, drastic mitochondrial damages and induction of tumor cell apoptosis. These data support the selection of TDMQ20 as drug-candidate against several human cancers.
已知癌细胞的增殖和转移依赖于血管生成，而血管生成受包括铜可用性在内的几个参数调节。四齿单喹啉（TDMQ）配体构成了一系列螯合剂，由于它们对铜（II）相对于铜（I）或其他生物金属（如铁或锌）具有特异性，因此专门用于调节铜稳态。其中一种螯合剂TDMQ20能有效抑制多种人类癌细胞系的增殖和迁移，比参考药物5-氟尿嘧啶效果更好，且相对于非癌人类细胞具有更高的选择性指数。TDMQ20的生物活性可能由铜的配位化学以及该螯合剂恢复铜稳态的能力及其随后的氧化还原性质驱动。TDMQ20的抗癌作用机制涉及细胞内活性氧的产生、严重的线粒体损伤和肿瘤细胞凋亡的诱导。这些数据支持选择TDMQ20作为针对多种人类癌症的候选药物。
