大环内酯类抗生素研究进展

The Advances of the Research on Macrolide Antibiotics

大环内酯类抗生素是一类化学结构和抗菌作用相近的药物。因其抗菌活性强、抗菌谱广、疗效显著和不易产生耐药性等优点而被广泛应用于临床。研究表明 ,大环内酯类抗生素能与细菌核糖体 50 s亚单位的 L 2 7及 L 2 2蛋白质结合 ,抑制细菌的蛋白合成而发挥抗菌作用。近年来 ,其家族新成员不断涌现 ,种类逐渐增多 ,并且新一代大环内酯类抗生素具有对酸稳定性好、半衰期长、组织药物浓度高等特点 ,不仅在感染性疾病治疗中起着极为重要的作用 ,而且在非感染性疾病发挥着独特的疗效。目前 ,其作用机制、构效关系、动力学特征和耐药机制逐渐被人们所认识 ,使这类药物的应用前景更加广阔。然而 ,大环内酯类抗生素有一定的毒性 ,尤其是静脉注射时会产生肾毒性、低血钾症和血栓性静脉炎等副作用 。

The macrolide antibiotics contain structurally and functionally similar drugs. They are widely used in the clinic due to their potent antibacterial activities, broad spectrum, obvious clinical efficacy and relatively low frequency of resistance. Studies showed that macrolide antibiotics exert antimicrobial effects by binding to L27 and L22 protein of the 50s subunit of bacterial ribosomes and inhibiting protein synthesis. Recently, their kinds are gradually increasing and new macrolide antibiotics have higher stability to acid,longer half life time,higher concentration in tissues than other old the macrolides. In the clinic,they play an important roles not only in infectious diseases but also in non-infectious diseases. Up to date, their mode of action and structure-function relationship, kinetic characters as well as resistant mechanisms are gradually understood, which lead to apply more widely. However,the macrolides are rather toxic, causing such serious side effects as renal failure, hypokalemia and thrombophlebitis, especially in intravenous administration.So the problems should be overcome in clinical application.