Marcfortine and Paraherquamide Class of Anthelmintics: Discovery of PNU- 141962

Title: Marcfortine and Paraherquamide Class of Anthelmintics: Discovery of PNU- 141962

Volume: 2 Issue: 7

Author(s): Patty L. McNally, Michael A. Mauragis, Michael F. Lipton, Veronica Wiley, Erich W. Zinser, John P. Davis, Susan J. Alexander-Bowman, Eileen M. Coscarelli, Carol A. Baker, Jerry W. Bowman, David G. Martin, Joyce I. Ciadella, Byung H. Lee, Gabe I. Kornis, Vincent P. Marshall, Christopher L. Haber, Howard D. Whaley, Timothy G. Geary, David P. Thompson, Sandra S. Johnson, Stephen J. Nelson, Fred E. Dutton and Michael F. Clothier

Affiliation:

Keywords: anthelmintic, marcfortine, paraherquamide, pnu-141962, nematocide

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 fivemembered 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.

Cite this article as:

McNally L. Patty, Mauragis A. Michael, Lipton F. Michael, Wiley Veronica, Zinser W. Erich, Davis P. John, Alexander-Bowman J. Susan, Coscarelli M. Eileen, Baker A. Carol, Bowman W. Jerry, Martin G. David, Ciadella I. Joyce, Lee H. Byung, Kornis I. Gabe, Marshall P. Vincent, Haber L. Christopher, Whaley D. Howard, Geary G. Timothy, Thompson P. David, Johnson S. Sandra, Nelson J. Stephen, Dutton E. Fred and Clothier F. Michael, Marcfortine and Paraherquamide Class of Anthelmintics: Discovery of PNU- 141962, Current Topics in Medicinal Chemistry 2002; 2 (7) . https://dx.doi.org/10.2174/1568026023393705