Copper in Medicine: Homeostasis, Chelation Therapy and Antitumor Drug Design

Wang, Tuo; Guo, Zijian

doi:10.2174/092986706776055742

Cited by 187 publications

(62 citation statements)

References 119 publications

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“…Although the human body requires copper in order to function, excessive intake can lead to drastic consequences. Some associated side effects include hepatitis, neurological disorders, kidney diseases, and Alzheimer's disease (137). The reason for this toxicity stems from the fact that copper can easily accept and donate single electrons to change oxidation states, thereby allowing it to catalyze toxic reactions, such as the in vivo reduction of hydrogen peroxide to form hydroxyl free radicals (138).…”

Section: The Pitfalls Of Click Chemistrymentioning

confidence: 99%

Click Chemistry, A Powerful Tool for Pharmaceutical Sciences

2008

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Abstract. Click chemistry refers to a group of reactions that are fast, simple to use, easy to purify, versatile, regiospecific, and give high product yields. While there are a number of reactions that fulfill the criteria, the Huisgen 1,3-dipolar cycloaddition of azides and terminal alkynes has emerged as the frontrunner. It has found applications in a wide variety of research areas, including materials sciences, polymer chemistry, and pharmaceutical sciences. In this manuscript, important aspects of the Huisgen cycloaddition will be reviewed, along with some of its many pharmaceutical applications. Bioconjugation, nanoparticle surface modification, and pharmaceutical-related polymer chemistry will all be covered. Limitations of the reaction will also be discussed.

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Section: The Pitfalls Of Click Chemistrymentioning

confidence: 99%

Click Chemistry, A Powerful Tool for Pharmaceutical Sciences

2008

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“…[2][3][4] For this reason, free cellular copper concentrations are maintained at extremely low levels. 5,6 Copper homeostasis in living organisms is actually highly regulated by both transcriptional control and selective transport mechanisms through a conserved group of proteins that contain unique cysteine-, methionine-and histidine-rich domains. 1 Altered levels of copper are associated with disease states, as established in the case of MD and WD, which are characterized by a deficiency or an overload of copper in the organism, respectively.…”

Section: Introductionmentioning

confidence: 99%

Copper in diseases and treatments, and copper‐based anticancer strategies

Tisato¹,

Marzano

Porchia³

et al. 2009

Medicinal Research Reviews

671

420

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Copper is found in all living organisms and is a crucial trace element in redox chemistry, growth and development. It is important for the function of several enzymes and proteins involved in energy metabolism, respiration, and DNA synthesis, notably cytochrome oxidase, superoxide dismutase, ascorbate oxidase, and tyrosinase. The major functions of copper-biological molecules involve oxidation-reduction reactions in which they react directly with molecular oxygen to produce free radicals. Therefore, copper requires tightly regulated homeostatic mechanisms to ensure adequate supplies without any toxic effects. Overload or deficiency of copper is associated, respectively, with Wilson disease (WD) and Menkes disease (MD), which are of genetic origin. Researches on Menkes and Wilson disorders have provided useful insights in the field of copper homeostasis and in particular into the understanding of intracellular trafficking and distribution of copper at molecular levels. Therapies based on metal supplementation with copper histidine or removal of copper excess by means of specific copper chelators are currently effective in treating MD and WD, respectively. Copper chelation therapy is now attracting much attention for the investigation and treatment of various neurodegenerative disorders such as Alzheimer, Parkinson and CreutzfeldtJakob. An excess of copper appears to be an essential co-factor for angiogenesis. Moreover, elevated levels of copper have been found in many types of human cancers, including prostate, breast, colon, lung, and brain. On these basis, the employment of copper chelators has been reported to be of therapeutic value in the treatment of several types of cancers as anti-angiogenic molecules. More recently, mixtures of copper chelators with copper salts have been found to act as efficient proteasome inhibitors and apoptosis inducers, specifically in cancer cells. Moreover, following the worldwide success of platinum(II) compounds in cancer chemotherapy, several families of individual copper complexes have been studied as potential antitumor agents. These investigations, revealing the occurrence of mechanisms of action quite different from platinum drugs, head toward the development of new anticancer metallodrugs with improved specificity and decreased toxic side effects.

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“…They form a variety of compounds with interesting spectroscopic and magnetic properties whose practical applications are the subject of ongoing research [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. In the cell, metals are usually found in their complexed form, either as standalone ions or inside specific planar carrier compounds encapsulated by proteins -e.g.…”

Section: Metal Ions In Natural Biological Systemsmentioning

confidence: 99%

Metal Ions Introduced to Proteins by Supramolecular Ligands

Woźnicka

Rybarska

Jagusiak

et al. 2017

Self-Assembled Molecules – New Kind of Protein Ligands

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Congo red and other supramolecular structures may intercalate various foreign compounds, particularly planar ones. Such hybrid ligands, acting as a unit, may attach themselves to proteins and penetrate into their interior, together with any intercalated substances. If the intercalant is a metal complexone, a stable metalloprotein may be formed. This chapter discusses intercalation of metal complexones with metal ions bound by supramolecular Congo red as a means of introducing contrast to amyloid-like aggregates in order to trace the initial stages of amyloidogenesis. We investigate the applicability of Titan yellow carrying silver ions, and the alizarin complexone carrying tungsten and lead ions.

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Copper in Medicine: Homeostasis, Chelation Therapy and Antitumor Drug Design

Cited by 187 publications

References 119 publications

Click Chemistry, A Powerful Tool for Pharmaceutical Sciences

Click Chemistry, A Powerful Tool for Pharmaceutical Sciences

Copper in diseases and treatments, and copper‐based anticancer strategies

Metal Ions Introduced to Proteins by Supramolecular Ligands

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