Design, syntheses, and characterization of piperazine based chemokine receptor CCR5 antagonists as anti prostate cancer agents
- Bioorg Med Chem Lett. 2014 May 15;24(10):2319-23. doi: 10.1016/j.bmcl.2014.03.073.
- 1. Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA.
- 2. Department of Chemistry, College of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
- 3. Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: [email protected].
Chemokine Receptor CCR5 plays an important role in the pro-inflammatory environment that aids in the proliferation of prostate Cancer cells. Previously, a series of CCR5 antagonists containing a piperidine ring core skeleton were designed based upon the proposed CCR5 Antagonist pharmacophore from molecular modeling studies. The developed CCR5 antagonists were able to antagonize CCR5 at a micromolar level and inhibit the proliferation of metastatic prostate Cancer cell lines. In order to further explore the structure-activity-relationship of the pharmacophore identified, the molecular scaffold was expanded to contain a piperazine ring as the core. A number of compounds that were synthesized showed promising anti prostate Cancer activity and reasonable cytotoxicity profiles based on the biological characterization.