Design and Synthesis of MAPK Inhibitors

Howard University, Washington DC

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Abstract

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.