Potential Therapeutic Applications of Metal Compounds Directed Towards Hypoxic Tissues

D.      Gambino

doi:10.2174/092986710793213797

Abstract

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.

Keywords: Hypoxia selectivity, metal-based compounds, bioreduction, bioreductive metal-based prodrugs, nitrogen mustards, aromatic N-oxides, quinoxalines and thiosemicarbazones metal complexes, Hypoxic Tissues, diagnostic medicinal purposes, medicinal purposes, solubility, lipophilicity, activation by bioreduction, magnetic resonance imaging (MRI), antitumoral activity of cisplatin, metal-based anticancer drugs, anticancer chemotherapy, organic chemotherapeutics, promoting metastasis and angiogenesis, slow-growing hypoxic solid tumors, hypoxia-selective cytotoxins, conventional antitumoral drugs, nitroaromatics, labile high-spin Co(II) octahedral complexes, sta-ble Co(II) hexaaquo species, bidentate ali-phatic nitrogen mustards, aerobic cytotoxicity, aziridine complexes, hypoxia selective cytotoxins, aliphatic mustards, polyazamacrocyclic nitrogen mustards, Nitrogen mustard ligands, bioreductive prodrugs, tetradentate polyazamacrocyclic nitrogen, pyrrolo[3,2-f]quinoline analogues, quantitative radiolytic, animal metastatic foci, redox cycling process, superoxide forma-tion, antecedent, Tirapazamine, bioreduction and radiotherapy, Chemo preventive, anti-tumor effects, vanadium-prodrug complex, normoxia, hypoxia, superoxide dismutase activity, Tirapazamine [62], Mitomycine C, Misonidazole, electrochemical behavior, hydrophilic solvents, Metal-Radionuclide Radiopharmaceuti-cals, diabetic retinopathy, radiodiagnosis, radiotherapy purposes, techniques gamma scintigraphy, annihilation radiation, Cu-bis(thiosemicarbazone) complexes, myocardium, potential radiotherapeutic agent, rapid acid-catalyzed dissociation, subsequent back-oxidation, PET tracers, necrotic tissue, hypoxia-selective nitroimidazoles, amineoxime-type chelators, non nitro-aryl-based ra-diotracer, novel potential hy-poxic-tissue tracers, Bioreduced in Biological Media, activated by bioreduction, chelating bioligands, antitumor agents, cisplatin, carboplatin, oxaliplatin, 2-methyl-5-nitro-imidazole derivatives, PnAO -1-(2-nitroimidazole), PnAO-5-0xa-6-(2-nitroimidazole), Pt(IV) complexes reduction potentials, anticancer agents, hypoxic solid tumors