Isolation and structure elucidation of Sch 642305, a novel bacterial DNA primase inhibitor produced by Penicillium verrucosum

J Nat Prod. 2003 Dec;66(12):1527-30. doi: 10.1021/np0302302.

Abstract

A novel primase inhibitor, Sch 642305 (1), was isolated from the fermentation broth of the fungal culture Penicillium verrucosum. The structure of 1 was elucidated on the basis of MS and NMR spectroscopic data as a new and unusual bicyclic 10-membered macrolide. The absolute configuration of the asymmetric centers was determined by X-ray crystallographic analysis of the p-bromobenzoate derivative (3). Compound 1 exhibited inhibitory activity against bacterial DNA primase enzyme with an EC(50) of 70 microM.

MeSH terms

  • Arizona
  • Crystallography, X-Ray
  • DNA Primase / antagonists & inhibitors*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology*
  • Fermentation
  • Macrolides / chemistry
  • Macrolides / isolation & purification*
  • Macrolides / pharmacology*
  • Molecular Conformation
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Penicillium / chemistry*

Substances

  • Enzyme Inhibitors
  • Macrolides
  • Sch 642305
  • DNA Primase