The natural product CCR5 antagonist anibamine and its analogs as anti-prostate cancer agents.

Abstract

Prostate cancer is a leading cause of death among males in the United States. As the chemokine receptor CCR5 is over-expressed in more aggressive forms of prostate cancer, and is also a critical receptor in inflammation, chemokine receptor CCR5 antagonists could potentially act as anti-prostate cancer agents. Anibamine, a natural product CCR5 antagonist, provides a unique molecular scaffold for the generation of novel analogs with possible anti-prostate cancer activity. A series of analogs of anibamine were designed, synthesized and tested against several prostate cancer cell lines. The analogs all acted as CCR5 antagonists at micromolar range affinity to the receptor while their anti-proliferative activity varied depending on the cell line type and their chemical structural properties. Further basal cytotoxicity characterization on these compounds indicated some of them may be suitable for in vivo studies.

• Authors: Kendra M Haney, Feng Zhang, Christopher K Arnatt, Yunyun Yuan, Guo Li, Joy L Ware, David A Gewirtz, Yan Zhang
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 21 Issue 18 Pg. 5159-63 (Sep 15 2011) ISSN: 1464-3405 [Electronic] England
• PMID: 21820898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Antineoplastic Agents
• Biological Products
• CCR5 Receptor Antagonists
• Pyridines
• Receptors, CCR5
• anibamine

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Biological Products (chemical synthesis, chemistry, pharmacology)
• CCR5 Receptor Antagonists
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Design
• Drug Screening Assays, Antitumor
• Humans
• Male
• Molecular Structure
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Pyridines (chemical synthesis, chemistry, pharmacology)
• Receptors, CCR5 (metabolism)
• Stereoisomerism
• Structure-Activity Relationship