title: Design, syntheses, and characterization of piperazine based chemokine receptor CCR5 antagonists as anti prostate cancer agents.
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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Arnatt
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Adams
authors.affiliation: Department of Chemistry, College of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA.
authors.forename: Kendra M
authors.initials: KM
authors.lastname: Haney
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA.
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D065100:CCR5 Receptor Antagonists; D010879:Piperazines
keywords: Antagonists; CCR5; Piperazine ring; Prostate cancer