Side chain modifications in lankacidin group antibiotics.

AUTOR(ES)

McFarland, J W

RESUMO

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.

Documentos Relacionados

• Dimerization and membrane anchors in extracellular targeting of vancomycin group antibiotics.
• Antibiotics.
• Toward an estimation of binding constants in aqueous solution: studies of associations of vancomycin group antibiotics.
• Pneumococcal resistance to antibiotics.
• Discrepancies between MBC and actual killing of viridans group streptococci by cell-wall-active antibiotics.