title: 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.affiliation: Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Kendra M
authors.initials: KM
authors.lastname: Haney
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Arnatt
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Yuan
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.forename: Joy L
authors.initials: JL
authors.lastname: Ware
authors.forename: David A
authors.initials: DA
authors.lastname: Gewirtz
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D065100:CCR5 Receptor Antagonists; D011725:Pyridines; D019713:Receptors, CCR5; C488244:anibamine