Incremental Conversion of Outer-Membrane Permeabilizers into Potent Antibiotics for Gram-Negative Bacteria

Cholic acid derivatives appended with amine groups have been prepared for use as permeabilizers of the outer membranes of Gram-negative bacteria. These compounds interact synergistically with antibiotics such as erythromycin and novobiocin to inhibit growth of Gram-negative bacteria. When a hydrophobic chain is included on the permeabilizers, they can be converted into potent antibiotics. The role of the hydrophobic chain is to facilitate self-promoted transport of the cholic acid derivatives across the outer membrane of Gram-negative bacteria. These compounds share activities found with polymyxin B and derivatives.