Incremental conversion of outer-membrane permeabilizers into potent antibiotics for Gram-negative bacteria

Cholic acid derivatives appended with amine groups have been prepared for u se as permeabilizers of the outer membranes of Gram-negative bacteria. Thes e compounds interact synergistically with antibiotics such as erythromycin and novobiocin to inhibit growth of Gram-negative bacteria. When a hydropho bic chain is included on the permeabilizers, they can be converted into pot ent antibiotics. The role of the hydrophobic chain is to facilitate self-pr omoted transport of the cholic acid derivatives across the outer membrane o f Gramnegative bacteria. These compounds share activities found with polymy xin B and derivatives.