Studies of the effects of antifungal cationic derivatives of amphotericin B on human erythrocytes.
The novel group of amphotericin B (AmB) cationic derivatives has been examined in terms of relationship between self-association and selective toxicity. In all determinations AmB has been used as reference compound. In vitro toxic effects of the compounds on human erythrocytes were determined by measuring leakage of intracellular potassium ions and hemolysis. Antifungal effects were determined as MIC and intracellular potassium loss. The compounds self-association was followed by UV-Vis spectroscopy. The results suggested that: i) unlike AmB the monomer/self-associated species ratio is not an essential in governing the selective toxicity of the derivatives studied; ii) the presence of a bulky substituent in the AmB molecule, preferably located at the amino group of mycosamine moiety is the structural factor essential for the selective toxicity improvement.
Slisz
Magdalena
M
Department of Pharmaceutical Technology and Biochemistry, Gdansk University of Technology, 11/12, Narutowicza St, 80-952 Gdansk, Poland.
Cybulska
Barbara
B
Mazerski
Jan
J
Grzybowska
Jolanta
J
Borowski
Edward
E
D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000633:toxicity; D000935:Antifungal Agents / Q000633:toxicity*; D002176:Candida albicans / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D011188:Potassium / Q000378:metabolism; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D000666:Amphotericin B; D011188:Potassium