THE INFLUENCE OF ELECTRIC CHARGE OF AROMATIC HEPTENE MACROLIDE ANTIBIOTICS ON THEIR ACTIVITY ON BIOLOGICAL AND LIPIDIC MODEL MEMBRANES

  • 1 January 1983
    • journal article
    • research article
    • Vol. 24  (2) , 270-276
Abstract
Natural aromatic heptaene macrolide antibiotics and their N-acyl and methyl ester derivatives [vacidin A, gedamycin, perimycin A, vacidin methyl ester, gedamycin methyl ester, N-N''-diacetyl vacidin, N''-acetyl gedamycin, N''-acetyl perimycin and N''succinyl perimycin], which differ mainly in their electric net charge, were compared for their efficiency in inducing yeast growth inhibition, [human] red blood cell lysis and increase in the ionic permeability of large unilamellar lipidic vesicles. Antifungal activity decreased in the following order: neutral .simeq. positively charged > negatively charged compounds. Hemolytic activity decreased in the order: neutral > negatively charged .mchgt. positively charged compounds. On lipidic model membranes, themselves either positively or negatively charged, electrostatic interaction had practically no influence on the efficiency of the differently charged antibiotics. On both biological and model systems, positively charged antibiotics were consistently more active on ergosterol-containing than on cholesterol-containing membranes, and were therefore considered as potentially good candidates for specific antifungal agents.