Marcfortine and paraherquamide class of anthelmintics: discovery of PNU-141962

Curr Top Med Chem. 2002 Jul;2(7):779-93. doi: 10.2174/1568026023393705.

Abstract

Three distinct chemical classes for the control of gastrointestinal nematodes are available: benzimidazoles, imidazothiazoles, and macrocyclic lactones. The relentless development of drug resistance has severely limited the usefulness of such drugs and the search for a new class of compounds preferably with a different mode of action is an important endeavor. Marcfortine A (1), a metabolite of Penicillium roqueforti, is structurally related to paraherquamide A (2), originally isolated from Penicillium paraherquei. Chemically the two compounds differ only in one ring; in marcfortine A, ring G is six-membered and carries no substituents, while in paraherquamide A, ring G is five-membered with methyl and hydroxyl substituents at C14. Paraherquamide A (2) is superior to marcfortine A as a nematocide. 2-Desoxoparaherquamide A (PNU-141962, 53) has excellent nematocidal activity, a superior safely profile, and is the first semi-synthetic member of this totally new class of nematocides that is a legitimate candidate for development. This review describes the chemistry, efficacy and mode of action of PNU-141962.

Publication types

  • Review

MeSH terms

  • Animals
  • Anthelmintics / chemical synthesis*
  • Anthelmintics / chemistry
  • Anthelmintics / therapeutic use
  • Humans
  • Indolizines / chemical synthesis*
  • Indolizines / chemistry
  • Indolizines / therapeutic use
  • Molecular Structure
  • Nematode Infections / drug therapy
  • Nematode Infections / prevention & control
  • Nematode Infections / veterinary
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Spiro Compounds / therapeutic use
  • Structure-Activity Relationship

Substances

  • 2-desoxoparaherquamide A
  • Anthelmintics
  • Indolizines
  • Spiro Compounds
  • marcfortine A
  • paraherquamide