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Various approaches have been developed for diminishing the effects of radiation on normal tissues or enhancing tumor cell killing by ionizing radiation. An important potential use for these agents is to modify the outcome of radiation therapy. Potential radioprotectors or radiosensitizers are organized in this review according to mechanism of action. Most of the agents studied are believed to act by reacting with DNA radicals that are produced within milliseconds of exposure to ionizing radiation. According to this mechanism, protectors restore a single electron to electron‐deficient radicals, preventing degradation of the structure of DNA, whereas sensitizers, such as molecular oxygen or nitroimidazoles, form adducts with these radicals, resulting in damage fixation. WR2721 (Ethyol) is the best‐characterized chemical radioprotector. Preferential activation of WR2721 in certain normal tissues by removal of a phosphate group provides a rationale for selective protection of these tissues. Cytokines and biological modifiers represent an important emerging class of radioprotectors that may be particularly useful in modifying bone marrow injury. Nitroimidazoles have been the most widely studied chemical radiosensitizers. Although clinical results with nitroimidazoles have not been impressive, the potential for this approach has not been fully explored, given that the doses that can be administered have been limited by drug toxicity and supplemental strategies, such as concurrent depletion of endogenous protectors, have not been explored in the clinic. Modifiers of tumor oxygenation represent an important class of radiosensitizers that are currently generating considerable clinical interest. RSR13, a modifier of the oxygen affinity of hemoglobin, is highlighted as an example of the process of drug development for this type of agent.
Various approaches have been developed for diminishing the effects of radiation on normal tissues or enhancing tumor cell killing by ionizing radiation. An important potential use for these agents is to modify the outcome of radiation therapy. Potential radioprotectors or radiosensitizers are organized in this review according to mechanism of action. Most of the agents studied are believed to act by reacting with DNA radicals that are produced within milliseconds of exposure to ionizing radiation. According to this mechanism, protectors restore a single electron to electron‐deficient radicals, preventing degradation of the structure of DNA, whereas sensitizers, such as molecular oxygen or nitroimidazoles, form adducts with these radicals, resulting in damage fixation. WR2721 (Ethyol) is the best‐characterized chemical radioprotector. Preferential activation of WR2721 in certain normal tissues by removal of a phosphate group provides a rationale for selective protection of these tissues. Cytokines and biological modifiers represent an important emerging class of radioprotectors that may be particularly useful in modifying bone marrow injury. Nitroimidazoles have been the most widely studied chemical radiosensitizers. Although clinical results with nitroimidazoles have not been impressive, the potential for this approach has not been fully explored, given that the doses that can be administered have been limited by drug toxicity and supplemental strategies, such as concurrent depletion of endogenous protectors, have not been explored in the clinic. Modifiers of tumor oxygenation represent an important class of radiosensitizers that are currently generating considerable clinical interest. RSR13, a modifier of the oxygen affinity of hemoglobin, is highlighted as an example of the process of drug development for this type of agent.
A new series of hydrogen bonding‐driven heterodimers have been self‐assembled in chloroform from hydrazide‐based monomers. Additional intermolecular donor‐acceptor interaction between the electron‐rich bis(p‐phenylene)‐34‐crown‐10 unit and the electron‐deficient naphthalene diimide unit has been utilized to increase the stability of the dimmers, and pronounced cooperativity of the two discrete non‐covalent forces to stabilize the dimer has been revealed by the quantitative 1H (2D) NMR and UV‐Vis experiments.
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