Highly substituted terphenyls as inhibitors of parasite cGMP-dependent protein kinase activity

J Nat Prod. 2006 Apr;69(4):710-2. doi: 10.1021/np0505418.

Abstract

Parasite cGMP-dependent protein kinase (PKG) is one of the validated biochemical targets for the treatment of coccidiosis. We screened our library of natural product extracts for inhibitors of parasite PKG for the discovery of anticoccidial leads. Terferol (1) and three new terphenyls (2, 3, and 4) were isolated using bioassay-guided fractionation of the microbial extract of a Phoma sp. by a high-throughput two-step isolation method employing LH-20 and reversed-phase HPLC. These compounds inhibited parasite PKG with IC(50) values in the range 0.9-5.8 microM.

MeSH terms

  • Animals
  • Ascomycota / chemistry*
  • Coccidiosis / drug therapy*
  • Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors*
  • Eimeria tenella / drug effects*
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / isolation & purification
  • Enzyme Inhibitors* / pharmacology
  • France
  • Molecular Structure
  • Terphenyl Compounds* / chemistry
  • Terphenyl Compounds* / isolation & purification
  • Terphenyl Compounds* / pharmacology

Substances

  • Enzyme Inhibitors
  • Terphenyl Compounds
  • terferol
  • Cyclic GMP-Dependent Protein Kinases