New antifungal antibiotics pradimicins FA-1 and FA-2: D-serine analogs of pradimicins A and C

J Antibiot (Tokyo). 1990 Oct;43(10):1223-9. doi: 10.7164/antibiotics.43.1223.

Abstract

Pradimicin FA-1 was produced via directed biosynthesis with substitution of D-serine for D-alanine in the 15-position of pradimicin A. This substitution was achieved by the addition of D-serine to the culture medium of Actinomadura hibisca P157-2. Likewise, pradimicin FA-2 was co-produced along with pradimicin FA-1 when the pradimicins A and C producing strain, A. hibisca A2493 was grown in D-serine-supplemented medium. The new pradimicin analogs share a common core structure of 5,6-dihydrobenzo[a]naphthacenequinone substituted by D-serine at C-15, but differ in the disaccharide moiety at C-5. Pradimicin FA-1 has an N-methylamino sugar and D-xylose. Pradimicin FA-2 is the des-N-methyl analog of pradimicin FA-1. The in vitro and in vivo antifungal activity of the analogs was comparable to that of pradimicin A.

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Anthracyclines*
  • Antibiotics, Antineoplastic / biosynthesis*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / metabolism*
  • Antibiotics, Antineoplastic / pharmacology
  • Antifungal Agents / biosynthesis*
  • Antifungal Agents / chemistry
  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacology
  • Candidiasis / drug therapy
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Fermentation
  • Fungi / drug effects*
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Inbred ICR
  • Molecular Structure
  • Nocardiaceae / metabolism*

Substances

  • Amino Acids
  • Anthracyclines
  • Antibiotics, Antineoplastic
  • Antifungal Agents
  • benanomicin B
  • pradimicin A
  • pradimicin FA 1
  • pradimicin FA 2