Quantitative structure-activity relationships in amphotericin B derivatives.
The quantitative structure-activity relationships studies of amphotericin B and its 16 semisynthetic derivatives obtained by modification at carboxyl and amino groups have been done. The results of five biological tests were subjected to principal component analysis, a numerical method useful in the investigation of large sets of data. For some compounds, also, interaction with lipidic vesicles was investigated by spectroscopic methods. The results obtained indicate that: (i) The presence of positively charged nitrogen atom (protonable or bearing fixed charge) is indispensable for biological activity and antibiotic-sterol interaction; (ii) The lack of free carboxyl group in the molecule favours the differentiation between cholesterol and ergosterol containing cells.
Chéron
M
M
Laboratoire de Physique et Chimie Biomoléculaire, CNRS (U.A. 198), Université Pierre et Marie Curie, Paris, France.
Cybulska
B
B
Mazerski
J
J
Grzybowska
J
J
Czerwiński
A
A
Borowski
E
E
D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004875:Ergosterol / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D011188:Potassium / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013329:Structure-Activity Relationship
D000666:Amphotericin B; D002784:Cholesterol; D011188:Potassium; D004875:Ergosterol