Chemistry and structure activity relationships of bafilomycin A1, a potent and selective inhibitor of the vacuolar H+-ATPase

Curr Med Chem. 1999 Dec;6(12):1197-212.


Bafilomycin A1, a macrolide antibiotic isolated from the fermentation of Streptomyces spp., is a potent and selective inhibitor of vacuolar-type proton translocating ATP-ases (V-ATPases) and was used to study the physiological role of this class of enzymes. An extensive chemical effort on the unusual structure of this macrolide led to the synthesis of significantly different bafilomycin derivatives. None of the new analogues was more potent than the parent compound but provided a significant amount of information about the structural requirements for the inhibitory activity of bafilomycin A1 in particular on chicken osteoclast (cOc) ATPase. The vinylic methoxy group adjacent to a carbonyl function, the dienic system and the hydroxy group at position 7 were recognized to be essential features for bafilomycin V-ATPase-inhibitory activity. This information was utilized to design simplified novel derivatives as inhibitors of bone resorption.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Drug Design
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Inhibitory Concentration 50
  • Macrolides*
  • Proton-Translocating ATPases / antagonists & inhibitors*
  • Proton-Translocating ATPases / metabolism
  • Streptomyces / chemistry
  • Structure-Activity Relationship
  • Vacuolar Proton-Translocating ATPases*


  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Macrolides
  • bafilomycin A1
  • Vacuolar Proton-Translocating ATPases
  • Proton-Translocating ATPases