Side chain modifications in lankacidin group antibiotics.
Novel N-acyl analogs of lankacidin may be prepared from 3-isocyanatolankone diformate [7,13-bis(formyloxy)-2-isocyanato-1,4,10,19-tetramethyl-16- oxabicyclo[13.2.2.]nonadeca-3,5,9,11-tetraen-17,18-dione]. Of seven such analogs evaluated in vitro only homolankacidin diformate showed significant activity. However, in a cell-free system two of the inactive analogs inhibited polypeptide synthesis as well as did lankacidin itself or erythromycin. Antibacterial activity, therefore, is a function of the ability of a congener to penetrate the bacterial cell membrane in addition to its intrinsic activity. Similarly, lankacidinol is as potent as lankacidin or erythromycin as an inhibitor of bacterial polypeptide synthesis in a cell-free system. This intrinsic activity is expressed as potent antibacterial activity against growing gram-positive cultures in O(2')-acyl derivatives with the proper lipophilicity.
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D007783:Lactones / Q000138:chemical synthesis / Q000494:pharmacology; D018942:Macrolides; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects
D000900:Anti-Bacterial Agents; D007783:Lactones; D018942:Macrolides; C008250:lankacidins