BACKGROUND: Due to anthelmintic resistance problems, there is a need to discover and develop new drugs for the treatment and control of economically important and pathogenic nematodes of livestock animals. With this focus in mind, we screened 236 compounds from a library (called the 'Kurz-box') representing chemically diverse classes such as heterocyclic compounds (e.g. thiazoles, pyrroles, quinolines, pyrimidines, benzo[1,4]diazepines), hydoxamic acid-based metalloenzyme inhibitors, peptidomimetics (bis- and tris-pyrimidoneamides, alkoxyamides) and various intermediates on Haemonchus contortus, one of the most important parasitic nematodes of ruminants. METHODS: In the present study, we tested these compounds, and measured the inhibition of larval motility and development of exsheathed third-stage (xL3) and fourth-stage (L4) larvae of H. contortus using an optimised, whole-organism phenotypic screening assay. RESULTS: Of the 236 compounds, we identified two active compounds (called BLK127 and HBK4) that induced marked phenotypic changes in the worm in vitro. Compound BLK127 induced an 'eviscerated' phenotype in the xL3 stage and also inhibited L4 development. Compound HBK4 exerted a 'curved' phenotype in both xL3s and L4s. CONCLUSIONS: The findings from this study provide a basis for future work on the chemical optimisation of these compounds, on assessing the activity of optimised compounds on adult stages of H. contortus both in vitro and in vivo (in the host animal) and against other parasitic worms of veterinary and medical importance.

• MeSH
• Anthelmintics chemistry   pharmacology   MeSH
• Phenotype MeSH
• Haemonchus drug effects   growth & development   MeSH
• Inhibitory Concentration 50 MeSH
• Larva drug effects   growth & development   MeSH
• Drug Evaluation, Preclinical MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The effects of condensed tannins (CTs) extracted from pine bark on egg hatching, larval development and the viability of infective L3 larvae of Trichostrongylus colubriformis (Giles, 1892) and Teladorsagia circumcincta (Stadelmann, 1894) (syn. Ostertagia circumcincta) were evaluated using in vitro bioassays. Significant inhibitory effects of CTs were obtained on the viability of the infective larvae, egg hatching and larval development of both nematodes. In all bioassays, the larval stages of Te. circumcincta were significantly (P < 0.05) more susceptible to the inhibitory effects of CT than those of Tr. colubriformis. At 1 000 microg/ml, CTs from pine bark inhibited 48% and 69% of the infective larvae of Tr. colubriformis and Te. circumcincta, respectively, from passing through the sieve relative to the control incubations (no CT added; P < 0.0001). At the same concentration, CTs were able to inhibit 36% and 47% of the eggs of the two parasites, respectively, from hatching relative to the control incubations without CTs. Moreover, at 150 microg/ml, the CTs were able to inhibit 88% and 95% (P < 0.0001 relative to control incubation) of L1 larvae of the two nematodes, respectively, from attaining the full development to L3 larvae in comparison with the control incubations without CTs. At 200 microg/ml, CTs were able to inhibit completely the larval development in both nematodes. Addition of 2 microg polyethylene glycol (PEG; tannin inhibitor) per microg CT eliminated up to 87% of the CT activity (P < 0.0001) compared to incubations without PEG. In conclusion, this study shows that CTs are able to disrupt the life cycle of nematodes and their effects varied according to the parasite species and stage.

• MeSH
• Pinus chemistry   MeSH
• Species Specificity MeSH
• Phylogeny MeSH
• Nematoda drug effects   MeSH
• Plant Bark chemistry   MeSH
• Larva drug effects   growth & development   physiology   MeSH
• Ovum drug effects   MeSH
• Motor Activity drug effects   MeSH
• Proanthocyanidins chemistry   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH