Recent understanding of oncogenesis suggests that correcting specific cell control elements that are altered in tumor cells would provide more selective and less toxic chemotherapeutic agents for cancer treatment and/or prevent. The mitogen-activated protein kinase (MAPK) pathway is one of the signaling processes that have been targeted for the development of novel anti-cancer agents. Specific inhibitors of enzymes in the MAP kinase cascades are candidates for the development of novel therapeutic agents for the treatment and/or prevention of cancer. Using classical synthesis and combinatorial solution phase parallel synthesis, the synthesis of imido-substituted and dithiocarbamyl-substituted 1,4-naphthoquinone and quinoline-5,8-dione analogs will be carried out. These compounds will be tested for their inhibitory activities on the Raf-1/Mek1/Map kinase 2/Erk2 signaling pathway. The anti-cancer properties of these compounds will also be investigated. These compounds are designed as potential Map kinase inhibitor leading to a new generation of anti-cancer agents. Our broad long-term objective for this application is to develop specific inhibitors of enzymes in the Map kinase signaling pathways that would be useful as therapeutic agents for cancer treatment and/or prevention.
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