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Potential Therapeutic Applications of Metal Compounds Directed Towards Hypoxic Tissues

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Medicinal Inorganic Chemistry offers the high diversity of metal coordination chemistry for the development of bioactive compounds for therapeutic or diagnostic medicinal purposes. The design of novel metal-based antitumor agents occupies a privileged position in this discovery process. On the other hand, the research on metal-based radiopharmaceuticals for therapy and imaging is a subarea of high priority and development. This review describes therapeutic applications of metal compounds directed towards hypoxic tissues. Strategies in the search for new bioreductive metal-based prodrugs will be discussed. In addition, approaches for the imaging of hypoxic tissues by using metal radionuclides will be exemplified.

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Keywords: 2-methyl-5-nitro-imidazole derivatives; Bioreduced in Biological Media; Chemo preventive; Cu-bis(thiosemicarbazone) complexes; Hypoxia selectivity; Hypoxic Tissues; Metal-Radionuclide Radiopharmaceuti-cals; Misonidazole; Mitomycine C; Nitrogen mustard ligands; PET tracers; PnAO -1-(2-nitroimidazole); PnAO-5-0xa-6-(2-nitroimidazole); Pt(IV) complexes reduction potentials; Tirapazamine; Tirapazamine 62; activated by bioreduction; activation by bioreduction; aerobic cytotoxicity; aliphatic mustards; amineoxime-type chelators; animal metastatic foci; annihilation radiation; antecedent; anti-tumor effects; anticancer agents; anticancer chemotherapy; antitumor agents; antitumoral activity of cisplatin; aromatic N-oxides; aziridine complexes; bidentate ali-phatic nitrogen mustards; bioreduction; bioreduction and radiotherapy; bioreductive metal-based prodrugs; bioreductive prodrugs; carboplatin; chelating bioligands; cisplatin; conventional antitumoral drugs; diabetic retinopathy; diagnostic medicinal purposes; electrochemical behavior; hydrophilic solvents; hypoxia; hypoxia selective cytotoxins; hypoxia selectivity; hypoxia-selective cytotoxins; hypoxia-selective nitroimidazoles; hypoxic solid tumors; hypoxic tissues; labile high-spin Co(II) octahedral complexes; lipophilicity; magnetic resonance imaging (MRI); medicinal purposes; metal-based anticancer drugs; metal-based compounds; myocardium; necrotic tissue; nitroaromatics; nitrogen mustards; non nitro-aryl-based ra-diotracer; normoxia; novel potential hy-poxic-tissue tracers; organic chemotherapeutics; oxaliplatin; polyazamacrocyclic nitrogen mustards; potential radiotherapeutic agent; promoting metastasis and angiogenesis; pyrrolo3,2-fquinoline analogues; quantitative radiolytic; quinoxalines and thiosemicarbazones metal complexes; radiodiagnosis; radiotherapy purposes; rapid acid-catalyzed dissociation; redox cycling process; slow-growing hypoxic solid tumors; solubility; sta-ble Co(II) hexaaquo species; subsequent back-oxidation; superoxide dismutase activity; superoxide forma-tion; techniques gamma scintigraphy; tetradentate polyazamacrocyclic nitrogen; vanadium-prodrug complex

Document Type: Research Article

Publication date: 2010-11-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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