Abstract：
We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae. Notably, hybrid 23Be demonstrated dual modes of action by inhibiting both protein synthesis and DNA replication in vitro and in vivo. Given these promising characteristics, 23Be emerges as a potential candidate for the treatment of community-acquired bacterial pneumonia.
摘要：
我们在此报告了将3-去克拉糖基克拉霉素与喹诺酮类通过延伸的二胺连接器连接的杂种的结构-活性关系。几个混血儿，以23Bc为例，23、23Bf,26Be,30BC，不仅恢复了对诱导耐药病原体的效力，而且还表现出对肺炎葡萄球菌和化脓性葡萄球菌组成型耐药菌株的活性显着增强，独立于克拉霉素或红霉素诱导而表达高水平抗性。此外,新型杂种对革兰氏阴性流感嗜血杆菌具有易感性。值得注意的是,杂交23Be通过在体外和体内抑制蛋白质合成和DNA复制而表现出双重作用模式。鉴于这些有希望的特征，23Be成为治疗社区获得性细菌性肺炎的潜在候选者。
