LABSO-Bio Laboratory, Department of Chemistry, Pontifical Catholic University of Rio de Janeiro, 225 Rua Marquês de, São Vicente, Brazil.
Institut Parisien de Chimie Moléculaire (IPCM), Sorbonne Université, CNRS, 4 place Jussieu, 75005, Paris, France.
Chembiochem. 2020 Sep 1;21(17):2474-2486. doi: 10.1002/cbic.202000122. Epub 2020 May 19.
This paper reports the design, synthesis and cytotoxicity studies of two new isoxazole-derived aroylhydrazone ligands and their dinuclear copper(II) complexes. Compounds were fully characterized by various spectroscopic and analytical techniques. The molecular structures of four derivatives were confirmed by X-ray crystallography. The stability of the ligands and the complexes in aqueous medium was monitored spectroscopically. Both the ligands and the complexes were shown to interact with calf thymus DNA (ct-DNA). Additionally, structures containing a phenol pendant arm were significantly more cytotoxic than those carrying a pendant pyridine substituent, reaching sub-micromolar IC values on the triple-negative human breast cancer cell line MDA-MB-231. The metal chelation and transchelation ability of the compounds towards Fe , Fe and Zn ions was explored as a possible mechanism of action of these compounds.
本文报道了两种新型异噁唑衍生的芳酰腙配体及其双核铜（II）配合物的设计、合成和细胞毒性研究。通过各种光谱和分析技术对化合物进行了充分的表征。通过 X 射线晶体学确定了四个衍生物的分子结构。通过光谱法监测了配体和配合物在水介质中的稳定性。结果表明，配体和配合物都与小牛胸腺 DNA（ct-DNA）相互作用。此外，含有苯环侧臂的结构比含有吡啶取代基的结构具有更高的细胞毒性，对三阴性人乳腺癌细胞系 MDA-MB-231 的 IC 值达到亚微摩尔级。还研究了化合物对 Fe 、Fe 和 Zn 离子的金属螯合和转金属螯合能力，作为这些化合物作用机制的一种可能。
