title: Anthelmintic cyclcooctadepsipeptides: complex in structure and mode of action.
abstract: The broad-spectrum anthelmintic cyclooctadepsipeptide PF1022A is a fungal metabolite from Rosellinia sp. PF1022, which is a Mycelia sterilia found on the leaves of Camellia japonica. A broad range of structurally related cyclooctadepsipeptides has been characterized and tested for anthelmintic activities. These metabolites have been used as starting points to generate semisynthetic derivatives with varying nematocidal capacity. Predominant among these compounds is emodepside, which exhibits a broad nematocidal potential against gastrointestinal and extraintestinal parasites. Here we review the chemical biology and mode of action of cyclooctadepsides with particular attention to PF1022A and emodepside. We illustrate how they target nematode neuromuscular function, opening up new avenues for antiparasitic treatments with potential capability for important selective toxicity.
authors.affiliation: Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krücken
authors.forename: Achim
authors.initials: A
authors.lastname: Harder
authors.forename: Peter
authors.initials: P
authors.lastname: Jeschke
authors.forename: Lindy
authors.initials: L
authors.lastname: Holden-Dye
authors.forename: Vincent
authors.initials: V
authors.lastname: O'Connor
authors.forename: Claudia
authors.initials: C
authors.lastname: Welz
authors.forename: Georg
authors.initials: G
authors.lastname: von Samson-Himmelstjerna
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D047630:Depsipeptides / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D009348:Nematoda / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000871:Anthelmintics; D029742:Caenorhabditis elegans Proteins; D047630:Depsipeptides; D051036:Large-Conductance Calcium-Activated Potassium Channels; C494845:slo-1 protein, C elegans; C075544:PF 1022A; C468987:emodepside