Isolation, structure and biological activities of platencin A(2)-A(4) from Streptomyces platensis

Bioorg Med Chem. 2010 Apr 1;18(7):2602-10. doi: 10.1016/j.bmc.2010.02.030. Epub 2010 Feb 23.

Abstract

Natural products serve as a great reservoir for chemical diversity and are the greatest source for antibacterial agents. Recent discoveries of platensimycin and platencin as inhibitors of bacterial fatty acid biosynthesis enzymes supplied new chemical scaffolds for potential antibacterial agents to overcome resistant pathogens. Discovery of natural congeners augment chemical modification in understanding of structure-activity relationship (SAR). Chemical and biological screening of the extracts led to isolation of three hydroxylated analogs of platencin. The C-12, C-14 and C-15 hydroxylated analogs showed attenuated activities which provided significant understanding of functional tolerance in the diterpenoid portion of the molecule. A truncated and oxidized C-13 natural congener was isolated which suggested direct intermediacy of ent-copalyl diphosphate for the biosynthesis of platensimycins and platencins.

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / chemistry
  • Adamantane / pharmacology
  • Aminobenzoates / chemistry*
  • Aminobenzoates / pharmacology
  • Aminophenols / chemistry*
  • Aminophenols / pharmacology
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Chromatography, High Pressure Liquid
  • Fermentation
  • Haemophilus influenzae / drug effects
  • Hydroxylation
  • Indicators and Reagents
  • Mass Spectrometry
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Conformation
  • Polycyclic Compounds / chemistry*
  • Polycyclic Compounds / pharmacology
  • Spectrophotometry, Ultraviolet
  • Staphylococcus aureus / drug effects
  • Streptomyces / chemistry*
  • Structure-Activity Relationship

Substances

  • Aminobenzoates
  • Aminophenols
  • Anti-Bacterial Agents
  • Indicators and Reagents
  • Polycyclic Compounds
  • platencin A2
  • platencin A3
  • platencin A4
  • Adamantane
  • platencin