Advances in the discovery and development of anthelmintics by harnessing natural product scaffolds

摘要: Widespread resistance to currently-used anthelmintics represents a major obstacle controlling parasitic nematodes of livestock animals. Given the reliance on in many control regimens, there is need for continued discovery and development new nematocides. Enabling such focus are: (i) chemical diversity natural products; (ii) availability curated, drug-like extract-, fraction- and/or compound-libraries from sources; (iii) utility practicality well-established whole-worm bioassays Haemonchus contortus-an important livestock-to screen product libraries; (iv) advanced chromatographic (HPLC), spectroscopic (NMR) spectrometric (MS) techniques bioassay-guided fractionation structural elucidation. This context provides sound basis identification characterisation anthelmintic candidates sources. chapter background importance impact helminth infections/diseases, parasite aspects drug discovery, reviews recent work focused screening well-defined compound libraries establish methods needed large-scale extract discovering plant marine extracts with nematocidal or nematostatic activity, purifying bioactive compounds assessing their potential further development; synthesising analogues selected purified possible 'lead' candidates. The describes some lessons learned this proposes future areas discovery. Collectively, findings show scaffolds as development. Developing via optimisation, efficacy safety evaluations, broad spectrum activity assessments, target an exciting prospect and, if successful, could pave way subsequent pre-clinical clinical evaluations.