Gagliardi S, Gatti P A, Belfiore P, Zocchetti A, Clarke G D, Farina C
SmithKline Beecham SpA, Via Zambeletti, 20021 Baranzate, Milano, Italy.
J Med Chem. 1998 May 21;41(11):1883-93. doi: 10.1021/jm9707838.
The macrolide antibiotic bafilomycin A1 is a highly potent and selective inhibitor of all the vacuolar ATPases (V-ATPases). With the aim of obtaining novel analogues specific for the osteoclast subclass of vacuolar ATPase, 31 derivatives of bafilomycin A1 were synthesized and tested for their ability to inhibit differentially the V-ATPase-driven proton transport in membrane vesicles derived from chicken osteoclasts (cOc) and bovine chromaffin granules (bCG). Although none of the new analogues were more potent than the parent compound, the obtained data provided a significant amount of information about the structural requirements for the inhibitory activity of bafilomycin A1. The different effects of a few analogues on the two enzymes could also suggest the possibility of a selective modulation of the V-ATPases in different tissues.
大环内酯类抗生素巴弗洛霉素A1是所有液泡型ATP酶（V-ATP酶）的高效选择性抑制剂。为了获得对液泡型ATP酶破骨细胞亚类具有特异性的新型类似物，合成了31种巴弗洛霉素A1的衍生物，并测试了它们对源自鸡破骨细胞（cOc）和牛嗜铬颗粒（bCG）的膜囊泡中V-ATP酶驱动的质子转运的差异抑制能力。尽管没有一种新类似物比母体化合物更有效，但所获得的数据提供了大量关于巴弗洛霉素A1抑制活性结构要求的信息。少数类似物对这两种酶的不同作用也表明了在不同组织中对V-ATP酶进行选择性调节的可能性。
