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1.
Bioorg Med Chem Lett ; 9(12): 1727-32, 1999 Jun 21.
Article in English | MEDLINE | ID: mdl-10397509

ABSTRACT

Following our discovery of the strong binding of thiadiazole 1 to the AF-2 neuropeptide receptor of gastrointestinal nematodes (e.g., Ascaris suum), we prepared two series of analogs. Only the series containing the thiadiazole ring had potencies comparable to that of compound 1. Analog 50 exhibited an apparent potency in the AF-2 binding assay 300 times that of compound 1.


Subject(s)
Anthelmintics/chemical synthesis , Helminth Proteins/metabolism , Neuropeptides/metabolism , Thiadiazoles/chemical synthesis , Animals , Anthelmintics/chemistry , Anthelmintics/pharmacology , Ascaris suum , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Helminth Proteins/drug effects , Neuropeptides/drug effects , Structure-Activity Relationship , Thiadiazoles/chemistry , Thiadiazoles/pharmacology
2.
Bioorg Med Chem Lett ; 8(23): 3317-20, 1998 Dec 01.
Article in English | MEDLINE | ID: mdl-9873726

ABSTRACT

We have prepared several anthelmintic coumarins based on the beta-hydroxyketoamide (BKA) template and have shown that this template remains valid over a wide range of changes to the coumarin moiety allowing for the inclusion of carbocyclic, bicyclic, and heterocyclic rings.


Subject(s)
Anthelmintics/chemical synthesis , Coumarins/chemical synthesis , Animals , Anthelmintics/pharmacology , Coumarins/pharmacology , Gerbillinae
3.
J Antibiot (Tokyo) ; 48(8): 820-3, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7592027

ABSTRACT

A novel cyclodepsipeptide of fungal origin, PF1022A, recently was reported to have anthelmintic activity. To supplement published reports and determine potential utility of PF1022A as a ruminant anthelmintic, the compound was examined in in vitro and in vivo models. Assays used measured motility of Haemonchus contortus (intrinsic drug potency), ATP levels (parasite death), and activity against H. contortus, Ostertagia ostertagi, and Trichostrongylus colubriformis in the jird (spectrum, potency, and efficacy by various routes). The potency of PF1022A in reducing motility is greater than commercial anthelmintics. Examination of ATP levels in PF1022A-paralyzed H. contortus indicates that worms are not killed, suggesting the compound acts as a neurotoxin in nematodes. In the jird, PF1022A has activity orally against each of the parasites studied and at doses comparable to all commercial anthelmintics, except the macrocyclic lactones which are more potent. Unfortunately, for some nematode species, parenteral delivery is ineffective at realistic doses.


Subject(s)
Anthelmintics/therapeutic use , Depsipeptides , Haemonchiasis/drug therapy , Peptides, Cyclic/therapeutic use , Adenosine Triphosphate/metabolism , Administration, Oral , Animals , Female , Gerbillinae , Haemonchus/drug effects , Molecular Structure , Ostertagia/drug effects , Trichostrongylus/drug effects
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