SYNTHESIS AND BIOLOGICAL EVALUATION OF SECOND GENERATION ANIBAMINE ANALOGUES AS NOVEL ANTI-PROSTATE CANCER AGENTS

• Main Author: Singh, Shilpa
• Format: Others
• Published: VCU Scholars Compass 2012
• Subjects: Medicinal Chemistry; Medicine and Health Sciences; Pharmacy and Pharmaceutical Sciences
• Online Access: http://scholarscompass.vcu.edu/etd/359; http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1358&context=etd

Prostate cancer is the most prevalent non-cutaneous cancer among men. Since the 19th century when Virchow first introduced the concept of inflammation in cancer, chemokines and their receptors have garnered a lot of interest. Chemokine receptor CCR5 has been especially implicated in many disease states and recently found to be over expressed in prostate cancer cell lines. Anibamine, a natural CCR5 antagonist discovered in 2004, has been found to have significant anti-prostate cancer activity at micromolar level. To optimize this compound and also discover a novel pharmacophore, exploration of the original structure was carried out. Significant modifications were made to the side chain in the original structure and ten different analogues were prepared by altering the original synthetic route. While cytotoxicity assay proved the compounds to be non toxic to normal cells, anti-proliferation assay displayed that having a bulky, hydrophobic group in the side chain of the parent compound is essential for the activity. Looking at this data, the third generation of analogues can be prepared that might generate a better lead compound for the treatment of prostate cancer.