Lipophilic 1,3-Xylyl-21-crown-6 Macrocyclic Polyether 2-Carboxylic Acids as Biological Mimics of the Ionophore Antibiotics

Article abstract of DOI:10.1021/jm00164a048

Twelve lipophilic 1,3-xylyl-21-crown-6 macrocyclic polyether 2-carboxylic acids (9a-9l), two lariat ether 1,3-xylyl-21-crown-6 macrocyclic polyether 2-carboxylic acids (21 and 22), and two 1,3-xylyl-28-crown-8 macrocyclic polyether 2-carboxylic acids (10a and 10b) were synthesized and tested for in vitro antibacterial activity, in vitro stimulation of rumen propionic acid production, and in vivo anticoccidial activity in chickens.These are biological screens relevant to animal health areas where the ionophore antibiotics such as monensin have found application.While the parent structure 1 without lipophilic substituents was biologically inactive, the lipophilic macrocycles were active in the two in vitro tests but not against chicken coccidiosis.One compound (9f) was tested in cattle and was found to increase levels of propionic acid in the rumen fermentation.This effect is considered an important factor for increasing the efficiency of feed utilization in cattle exhibited by the ionophore antibiotic monensin.The alkali ion salts of these lipophilic macrocyclic polyether carboxylic acids are very soluble in organic solvents and insoluble in water.These compounds are proposed to act as ion-transport agents and functional mimics of the ionophore antibiotics in the biological systems described above.