title: Isoxazolines: A Novel Chemotype Highly Effective on Ectoparasites.
abstract: Efficient control of arthropod ectoparasite infestations has a long-standing history in the agriculture and veterinary sectors, aiming to decrease the parasite burden of affected crops and animals. Ligand-gated chloride channels (LGCCs) modulated by γ-aminobutyric acid (GABA) and glutamate have been identified as suitable molecular targets, and several classes of potent parasiticides have been devised. Due to the increase in cross-resistance and decreased development of new chemical entities, an urgent need for new parasiticides or prevention schemes has emerged. In the last decade, an innovative isoxazoline chemotype appears to offer promise for inhibiting LGCCs with a new mode of action and distinct binding site from that of historical agents. Considerable efforts have focused on optimizing the antiparasitic activity of isoxazolines and may provide the potential for future human use.
authors.affiliation: Marie Curie Initial Training Network "ParaMet", Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Tina
authors.initials: T
authors.lastname: Weber
authors.affiliation: Boehringer Ingelheim Animal Health GmbH, Binger Straße 173, 55216, Ingelheim am Rhein, Germany. paul.selzer@boehringer-ingelheim.com.|Universität Tübingen, Interfakultäres Institut für Biochemie, Tübingen, Germany. paul.selzer@boehringer-ingelheim.com.|Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, Faculty of Biomedical & Life Sciences, University of Glasgow, Glasgow, UK. paul.selzer@boehringer-ingelheim.com.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Selzer
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D018698:Glutamic Acid / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000977:Antiparasitic Agents; D018118:Chloride Channels; D007555:Isoxazoles; C109777:glutamate-gated chloride channels; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: arthropod-borne diseases; drug discovery; ectoparasiticides; ion channels; isoxazolines