Dipartimento di Scienze Chimiche e Geologiche, Università di Cagliari, Cittadella Universitaria, 09042 Monserrato-Cagliari, Italy.
J Inorg Biochem. 2014 Jan;130:112-21. doi: 10.1016/j.jinorgbio.2013.09.022. Epub 2013 Oct 18.
Attention is devoted to the role of chelating agents in the treatment of aluminium related diseases. In fact, in spite of the efforts that have drastically reduced the occurrence of aluminium dialysis diseases, they so far constitute a cause of great medical concern. The use of chelating agents for iron and aluminium in different clinical applications has found increasing attention in the last thirty years. With the aim of designing new chelators, we synthesized a series of kojic acid derivatives containing two kojic units joined by different linkers. A huge advantage of these molecules is that they are cheap and easy to produce. Previous works on complex formation equilibria of a first group of these ligands with iron and aluminium highlighted extremely good pMe values and gave evidence of the ability to scavenge iron from inside cells. On these bases a second set of bis-kojic ligands, whose linkers between the kojic chelating moieties are differentiated both in terms of type and size, has been designed, synthesized and characterized. The aluminium(III) complex formation equilibria studied by potentiometry, electrospray ionization mass spectroscopy (ESI-MS), quantum-mechanical calculations and (1)H NMR spectroscopy are here described and discussed, and the structural characterization of one of these new ligands is presented. The in vivo studies show that these new bis-kojic derivatives induce faster clearance from main organs as compared with the monomeric analog.
本文致力于研究螯合剂在治疗与铝相关疾病中的作用。事实上，尽管已经采取了大量措施来大幅减少铝透析疾病的发生，但它们仍然是一个令人高度关注的医学问题。在过去的三十年中，螯合剂在不同的临床应用中用于铁和铝的研究受到了越来越多的关注。为了设计新型螯合剂，我们合成了一系列含有两个通过不同连接体连接的 kojic 单元的 kojic 酸衍生物。这些分子的一个巨大优势是它们便宜且易于生产。之前对这组配体中第一组与铁和铝的配合物形成平衡的研究表明，它们具有非常好的 pMe 值，并证明了它们能够从细胞内部清除铁。在此基础上，我们设计、合成并表征了第二组双 kojic 配体，这些配体的 kojic 螯合部分之间的连接体在类型和大小上都有所不同。本文详细描述和讨论了通过电位法、电喷雾电离质谱（ESI-MS）、量子力学计算和（1）H NMR 光谱研究的铝（III）配合物形成平衡，并介绍了其中一种新型配体的结构特征。体内研究表明，与单体类似物相比，这些新的双 kojic 衍生物能更快地从主要器官中清除。
