Synthesis and Evaluation of Anibamine and Its Analogs as Novel Anti-Prostate Cancer Agents

• Main Author: Haney, Kendra
• Format: Others
• Published: VCU Scholars Compass 2009
• Subjects: CCR5; Prostate Cancer; Anibamine; Synthesis; Chemicals and Drugs; Medicine and Health Sciences
• Online Access: http://scholarscompass.vcu.edu/etd/1974; http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=2973&context=etd

The chemokine receptor CCR5 has been implicated in the pathogenesis of prostate cancer. A novel natural product, anibamine, was isolated and found to be a micromolar inhibitor of the receptor. Anibamine was used as a new anti-prostate cancer lead compound. To discover the pharmacophore, analogs of anibamine were designed using the “deconstruction-reconstruction-elaboration” approach and synthesized. The establishment of a stereoselective route to only one isomer was explored, to increase yield and eliminate elaborate purification procedures. Analogs were found to have anti-prostate cancer activity at levels higher than the parent compound. The molecular modeling studies of the deconstructed analogs indicate that due to the psuedo-symmetry of the parent compound, the binding conformation of the deconstructed analogs may not be very different from each other. All this information together may help identify a next generation lead compound for anti-prostate cancer treatment.