Cholic acid derivatives: novel antimicrobials

Mimics of squalamine and polymyxin B (PMB) have been prepared from cholic a cid in hope of finding new antimicrobial agents. The squalamine mimics incl ude the polyamine and sulphate functionalities found in the parent antibiot ic, however, the positions relative to the steroid nucleus have been exchan ged. The PMB mimics include the conservation of functionality among the pol ymyxin family of antibiotics, the primary amine groups and a hydrophobic ch ain. Although the squalamine and PMB mimics are morphologically dissimilar, they display similar activities. Both are simple to prepare and demonstrat e broad spectrum antimicrobial activity against Gram-negative and Gram-posi tive organisms. Specific examples may be inactive alone, yet effectively pe rmeabilise the outer membranes of Gram-negative bacteria rendering them sen sitive to hydrophobic antibiotics. Problems associated with some of the squ alamine and PMB mimics stem from their haemolytic activity and interactions with serum proteins, however, examples exist without these side effects wh ich can sensitise Gram-negative bacteria to hydrophobic antibiotics.