Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Bioorg Med Chem. 2020 Aug 15;28(16):115604. doi: 10.1016/j.bmc.2020.115604. Epub 2020 Jun 30.
Geranylgeranyl diphosphate synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma. A series of bisphosphonates linked to an isoprenoid tail through an amide linkage has been prepared and tested for the ability to inhibit GGDPS in enzyme and cell-based assays. The amides were designed as analogues to triazole-based GGDPS inhibitors. Several of the new compounds show GGDPS inhibitory activity in both enzyme and cell assays, with potency dependent on chain length and olefin stereochemistry.
香叶基香叶基二磷酸合酶 (GGDPS) 抑制剂因其对骨髓癌多发性骨髓瘤的活性而具有潜在的治疗意义。已经制备了一系列通过酰胺键连接到异戊二烯尾部的双膦酸盐，并测试了它们在酶和基于细胞的测定中抑制 GGDPS 的能力。酰胺被设计为三唑基 GGDPS 抑制剂的类似物。一些新化合物在酶和细胞测定中均显示出 GGDPS 抑制活性，其效力取决于链长和烯烃立体化学。
