Baginski M, Czub J
Department of Pharmaceutical Technology and Biochemistry, Gdansk University of Technology, Poland.
Curr Drug Metab. 2009 Jun;10(5):459-69. doi: 10.2174/138920009788898019.
Amphotericin B (AmB) is a well known antifungal and antiprotozoal antibiotic used in the clinic for several decades. Clinical applications of AmB, however, are limited by its nephrotoxicity and many other acute side effects which are not acceptable by patients when their life is not threaten. In order to improve the therapeutic index of this drug, lipid formulations have been introduced and many efforts have been made to obtain less toxic AmB derivatives by chemical modifications of the parent drug. This review presents concise knowledge about this fascinating compound and a critical review of the data published within last few years about the mechanism of action of this antibiotic. In particular, in the present work we discuss: i) structure and properties of AmB and its recently synthesized new derivatives; ii) antifungal and antileishmanial activity and toxicity of these compounds; and iii) mode of action of AmB and its derivatives at cellular and molecular levels, with particular attention paid to interactions of AmB and different components of cellular membranes.
两性霉素B（AmB）是一种广为人知的抗真菌和抗原虫抗生素，已在临床上使用了几十年。然而，AmB的临床应用受到其肾毒性和许多其他急性副作用的限制，在患者生命未受到威胁时，这些副作用是患者无法接受的。为了提高这种药物的治疗指数，已经引入了脂质制剂，并做出了许多努力，通过对母体药物进行化学修饰来获得毒性较小的AmB衍生物。本综述介绍了关于这种迷人化合物的简明知识，并对过去几年发表的关于这种抗生素作用机制的数据进行了批判性综述。特别是，在本工作中，我们讨论：i）AmB及其最近合成的新衍生物的结构和性质；ii）这些化合物的抗真菌和抗利什曼原虫活性及毒性；iii）AmB及其衍生物在细胞和分子水平的作用方式，特别关注AmB与细胞膜不同成分的相互作用。
