A multidisciplinary effort is underway to design and synthesize (a) an antineoplastic agent effective against slow growing tumors, and (b) a radiosensitizing agent to selectively sensitize hypoxic tumor cells towards treatment with radiation. Triphenylphosphinegold complex of thymidine has been shown in our preliminary experiments to possess potent antineoplastic activity against P388 leukemia and B16 melanoma. Attempts will be made to delineate the biochemical mechanism(s) of action of this agent, and to design and synthesize a series of purine and pyrimidine analog complexes to increase the antineoplastic activity. Development of radiosensitizers has been undertaken to overcome the problem of radioresistance of hypoxic cells present in tumors toward ionizing radiation. An extensive structure activity relationship study is being carried out for nitroimidazole analogs in an attempt to reduce the CNS toxicity and increase therapeutic efficacy. To this end, a variety of 2-nitroimidazole nucleosides will be synthesized and tested for radiosensitization by in vitro and in vivo techniques.