2. Academic Validation
  3. Design, syntheses, and characterization of piperazine based chemokine receptor CCR5 antagonists as anti prostate cancer agents

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.
Christopher K Arnatt 1,  Joanna L Adams 1,  Zhu Zhang 2,  Kendra M Haney 1,  Guo Li 1,  Yan Zhang 3
Affiliations

Affiliations

  • 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: yzhang2@vcu.edu.
PMID: 24731275 DOI: 10.1016/j.bmcl.2014.03.073
Abstract

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.

Keywords

Antagonists; CCR5; Piperazine ring; Prostate cancer.

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