Sythesis and Biological Screening of a Series of Novel Chemokine Receptor CCR5 Antagonists

The chemokine receptor CCR5 has been implicated in the pathogenesis of cancers and AIDS. A series of novel piperidine derivatives were designed, synthesized, and evaluated as CCR5 antagonists. The ability of the new ligands to inhibit the increment of intracellular calcium level stimulated by endogenous ligand CCL5 was measured in the calcium mobilization assay as an indication of its CCR5 receptor antagonism. The anti-proliferation assay was performed to measure the ability of these new compounds to inhibit the proliferation of prostate cancer cell lines, PC-3 and M12. A new lead compound has been identified which showed micromolar level of inhibition to PC-3 cell line proliferation as well as calcium mobilization. These studies are the beginning of a thorough analysis of the CCR5 receptor antagonist binding pocket in the CCR5 receptor. Further examination may help identify next generation lead to develop highly selective CCR5 receptor antagonists and anti prostate cancer agents.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Pharmaceutical Sciences

Year dc:date.available

2011

Author dc:creator

• Vaithianathan, Soundarya

Contributors dc:contributor

• Yan Zhang

• Medicine and Health Sciences
• Pharmacy and Pharmaceutical Sciences

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/243

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-1242