Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada.
Molecular and Environmental Sciences Research Group, Department of Geological Sciences, University of Saskatchewan, SK S7N 5E2, Canada; Department of Chemistry, University of Saskatchewan, SK S7N 5C9, Canada.
J Inorg Biochem. 2014 Apr;133:50-6. doi: 10.1016/j.jinorgbio.2014.01.003. Epub 2014 Jan 16.
Clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) recently has shown promising results in the treatment of Alzheimer's disease and in cancer therapy, both of which also are thought to be due to clioquinol's ability as a lipophilic copper chelator. Previously, clioquinol was used as an anti-fungal and anti-protozoal drug that was responsible for an epidemic of subacute myelo-optic neuropathy (SMON) in Japan during the 1960s, probably a myeloneuropathy arising from a clioquinol-induced copper deficiency. Previous X-ray absorption spectroscopy of solutions of copper chelates of clioquinol suggested unusual coordination chemistry. Here we use a combination of electron paramagnetic, UV-visible and X-ray absorption spectroscopies to provide clarification of the chelation chemistry between clioquinol and copper. We find that the solution structures for the copper complexes formed with stoichiometric and excess clioquinol are conventional 8-hydroxyquinolate chelates. Thus, the promise of clioquinol in new treatments for Alzheimer's disease and in cancer therapy is not likely to be due to any novel chelation chemistry, but rather due to other factors including the high lipophilicity of the free ligand and chelate complexes.
近年来，弹性蛋白（5-氯-7-碘-8-羟基喹啉）在治疗老年痴呆症和癌症方面显示出了有前景的效果，这两种疾病也被认为是由于弹性蛋白作为亲脂性铜螯合剂的能力。此前，弹性蛋白曾被用作抗真菌和抗原生动物药物，在 20 世纪 60 年代的日本导致了亚急性骨髓视神经病变（SMON）的流行，可能是一种由弹性蛋白诱导的铜缺乏引起的骨髓神经病。先前对弹性蛋白铜配合物溶液的 X 射线吸收光谱研究表明，其配位化学具有不寻常性。在这里，我们使用电子顺磁共振、紫外可见和 X 射线吸收光谱学的组合，为弹性蛋白与铜之间的螯合化学提供了澄清。我们发现，与等摩尔和过量弹性蛋白形成的铜配合物的溶液结构是常规的 8-羟基喹啉螯合物。因此，弹性蛋白在治疗老年痴呆症和癌症方面的新治疗方法的前景不太可能归因于任何新颖的螯合化学，而是归因于其他因素，包括游离配体和螯合物的高亲脂性。
