Bafilomycin a1

The family of bafilomycins belongs to the macrolide antibiotics produced by a large number of streptomyces. Their chemical structure is defined by a 16-membered lactone ring skeleton. Bafilomycins A1, B1 and C1 were first isolated from Streptomyces griseus in 1983. During a screening to identify microbial secondary metabolites whose activity mimicked that of two cardiac glycosides, bafilomycin C1 was identified as an inhibitor of P-ATPase.

Bafilomycins show a wide range of biological activities: they are antiproliferative, antiparasitic, immunosuppressive and antifungal. Bafilomycin C1 has been found to have activity against Caenorhabditis elegans, ticks and tapeworms and additionally stimulates the release of γ amino butyric acid (GABA) from rat synaptosomes. Independently of this, bafilomycin A1 and other derivatives have been isolated from S. griseus and have been shown to have antibiotic activity against some yeasts, gram-positive bacteria and fungi.

The most commonly used antibiotic of the bafilomycin family is bafilomycin A1 (chemical formula: C35H58O9), an effective inhibitor of cellular autophagy. Bafilomycin A1 shows cytotoxicity at high concentrations in a variety of cancers. In particular, Bafilomycin A1 induces caspase-independent cell death in HCC cells. Bafilomycin A1 acts specifically on the V-ATPase. It can therefore be described as an inhibitor of V-ATPase (vacuolar-type H+ ATPase). At higher micromolar concentrations, Bafilomycin A1 also acts on P-type ATPases, which have a phosphorylated transition state. Bafilomycin A1 serves as an important tool compound in many in vitro research applications. However, the clinical application is limited by a considerable toxicity profile.

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