Marcfortine and Paraherquamide Class of Anthelmintics: Discovery of PNU- 141962
Authors: Lee, B.H.; Clothier, M.F.; Dutton, F.E.; Nelson, S.J.; Johnson, S.S.; Thompson, D.P.; Geary, T.G.; Whaley, H.D.; Haber, C.L.; Marshall, V.P.; Kornis, G.I.; McNally, P.L.; Ciadella, J.I.; Martin, D.G.; Bowman, J.W.; Baker, C.A.; Coscarelli, E.M.; Alexander-Bowman, S.J.; Davis, J.P.; Zinser, E.W.; Wiley, V.; Lipton, M.F.; Mauragis, M.A.
Source: Current Topics in Medicinal Chemistry, Volume 2, Number 7, 1 June 2002 , pp. 779-793(15)
Publisher: Bentham Science Publishers
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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.Keywords: anthelmintic; marcfortine; paraherquamide; pnu-141962; nematocide
Document Type: Review article
DOI: 10.2174/1568026023393705
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