人用妙林类抗生素开发新进展

Progress in the development of mutilin antibiotics used in human

随着细菌耐药现象的日益严重,从天然产物中寻找抗菌机制独特的先导化合物已成为新型抗菌药物开发的重要手段。因此,先前未被开发作为人类使用的兽用抗菌药物也得到了重新评估。妙林类抗生素是由担子菌产生的一种三环二萜类化合物,主要作用于50S核糖体亚基,通过抑制肽基转移酶的活性而使细菌的蛋白质合成受阻,其中主要代表药物泰妙菌素和沃尼妙林作为兽用抗生素已被广泛使用。新近衍生物retapamulin作为人用抗生素成功上市,实现了妙林类化合物从兽用抗生素到人用抗生素的飞跃,掀起了新型人用妙林类化合物研究开发的浪潮。文中着重就2004-2008年人用妙林类抗生素的开发以及专利的相关最新进展进行简要综述。

The emergence of muhi-drug-resistant microorganisms leads to a concerted search for leading compounds with particular antibacterial modes of action and activity derived from natural products. Therefore, previously discovered classes of veterinary antibacterial agents that have not been used in humans are also reassessed. Mutilins belong to the family of tricyclic diterpenoids, originally isolated from the basidiomycetes; these conlpounds inhibit bacterial protein synthesis by specifically targeting the large subunit （50S） of the bacterial ribosome. The representative agents, tiamulin and valnemulin, have been widely used as veterinary antibiotics. The successful market of the novel derivative retapamulin stands for a great progress in developing veterinary antibiotics to the antibiotics used in human, and raises the tidal wave of the development of mutilins. This article provided an overview of mutilins used in human, and described recent advances in the drug development and patents during 2004 - 2008.