Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, USA.
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5159-63. doi: 10.1016/j.bmcl.2011.07.058. Epub 2011 Jul 23.
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.
前列腺癌是美国男性死亡的主要原因之一。由于趋化因子受体 CCR5 在更具侵袭性的前列腺癌中过表达，并且也是炎症中的关键受体，因此趋化因子受体 CCR5 拮抗剂可能具有作为抗前列腺癌药物的潜力。Anibamine 是一种天然的 CCR5 拮抗剂，为新型类似物的生成提供了独特的分子骨架，这些类似物可能具有抗前列腺癌活性。设计、合成了一系列 anibamine 的类似物，并对几种前列腺癌细胞系进行了测试。这些类似物对受体的亲和力均在微摩尔范围内，表现为 CCR5 拮抗剂，而它们的抗增殖活性则取决于细胞系类型及其化学结构特性。对这些化合物进行进一步的基础细胞毒性特征分析表明，其中一些可能适合进行体内研究。
