Quantitative structure-activity relationships in amphotericin B derivatives

Biochem Pharmacol. 1988 Mar 1;37(5):827-36. doi: 10.1016/0006-2952(88)90168-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / analogs & derivatives*
  • Amphotericin B / pharmacology
  • Candida albicans / drug effects
  • Cholesterol / blood
  • Dose-Response Relationship, Drug
  • Ergosterol / metabolism
  • Erythrocytes / drug effects
  • Hemolysis
  • Humans
  • Potassium / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Structure-Activity Relationship

Substances

  • Amphotericin B
  • Cholesterol
  • Potassium
  • Ergosterol