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

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.

journal_name

Curr Top Med Chem

authors

Lee BH,Clothier MF,Dutton FE,Nelson SJ,Johnson SS,Thompson DP,Geary TG,Whaley HD,Haber CL,Marshall VP,Kornis GI,McNally PL,Ciadella JI,Martin DG,Bowman JW,Baker CA,Coscarelli EM,Alexander-Bowman SJ,Davis JP,Zinser E

doi

10.2174/1568026023393705

keywords:

subject

Has Abstract

pub_date

2002-07-01 00:00:00

pages

779-93

issue

7

eissn

1568-0266

issn

1873-4294

journal_volume

2

pub_type

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