Potential Therapeutic Applications of Metal Compounds Directed Towards Hypoxic Tissues

D.      Gambino

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