We propose to investigate a completely novel series of agents that have never been applied to cancer therapy. There is currently no curative therapy for advanced prostate cancer; available treatments are aimed at slowing the spread of the disease and relieving symptoms. Thus, nearly one-third of all men diagnosed with prostate cancer (i.e., about 60,000 men per year) undergo surgery from which they are unlikely to benefit. Surgery and radiation therapy are options for cancer that is confined to the prostate. In preliminary studies, we have shown some new drugs prepared in our laboratory to inhibit the proliferative growth of prostate cancer cells. Studies proposed herein are designed to test the hypothesis that the activity of this new class of drugs can be optimized, and this should lay the groundwork for development of a new class of therapeutic agents to treat advanced aggressive prostate cancer. This is a high-risk, innovative proposal to discover a nonsurgical means of management for localized disease and for a more selective and curative pharmacologic therapy for advanced prostate cancer.