Copper and iron complexes with antitumour activity

被引:15
作者
Easmon, J [1 ]
机构
[1] Univ Innsbruck, Pharmaceut Chem Dept, Inst Pharm, A-6020 Innsbruck, Austria
关键词
antibodies; antigens; bacterial siderophores; bioconjugates; biomimetic oxidation catalysts; cancer chemotherapy; cationic metalloporphyrins; ceruloplasmin; clays; copper complexes; copper and iron transport genes; cytotoxicity; iron complexes; magnetically targeted carrier metallo-drugs; photodynamic therapy; photosensitisers; polyaza macrocyclic ligands; prostrate specific antigen; reactive oxygen species; superoxide dismutase; superoxide dismutase mimics; telomerase inhibitors; zeolites;
D O I
10.1517/13543776.12.6.789
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Copper and iron although present in small amounts in the body, are vital for the normal functioning of several enzymes and proteins involved in energy metabolism, respiration and DNA synthesis. Their ionic forms are prone to participate in one-electron transfer reactions and can thereby catalyse redox reactions. However, this capacity enables copper and iron to generate free radicals, which may activate signalling pathways for cell proliferation. Evidence obtained over the years has shown that cancer cells generally require more copper and iron for their growth and metabolism than normal resting cells. Therefore, agents that affect copper and iron homeostasis in the cell are of considerable interest for cancer therapy. Several approaches have been pursued to achieve this goal; i) the identification of new iron binding bacterial siderophores, such as the exochelins and myochelins, with better physicochemical properties than desferrioxamine, ii) the development of macrocyclic polydentate amine ligands with high binding capacity for copper or iron ions compared to other trace elements. The macrocylic chelators have been found to have enhanced in vivo stability compared to the acyclic chelators, iii) the introduction of the antioxidant dithiocarbamate and analogues as radical scavenging agents in combination therapy to reduce the side effects of anticancer agents. These compounds mediate their action in vivo by binding copper and iron ions, iv) the development of a variety of metal chelating photosensitisers, such as the boronated porphyrins, cationic porphyrins, chlorins, phthalocyanins, porphyrins and texapyrins, suitable for use in photodynamic therapy. These compounds have the ability to accumulate to greater levels in tumour tissues than nontumour tissues. In general, the metal chelating agents can be administered alone, chelated to a radioactive or nonradioactive metal to facilitate tumour imaging, diagnosis and or treatment.
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页码:789 / 818
页数:30
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