Weber Tina, Selzer Paul M
Marie Curie Initial Training Network "ParaMet", Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Boehringer Ingelheim Animal Health GmbH, Binger Straße 173, 55216, Ingelheim am Rhein, Germany.
ChemMedChem. 2016 Feb 4;11(3):270-6. doi: 10.1002/cmdc.201500516. Epub 2016 Jan 6.
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.
在农业和兽医领域,有效控制节肢动物体外寄生虫侵扰有着悠久的历史,目的是减轻受影响农作物和动物的寄生虫负担。由γ-氨基丁酸(GABA)和谷氨酸调节的配体门控氯离子通道(LGCCs)已被确定为合适的分子靶点,并且已经设计出几类有效的杀寄生虫剂。由于交叉抗性增加以及新化学实体开发减少,迫切需要新的杀寄生虫剂或预防方案。在过去十年中,一种创新的异恶唑啉化学类型似乎有望以一种新的作用模式抑制LGCCs,且其结合位点与传统药物不同。大量努力集中在优化异恶唑啉的抗寄生虫活性上,这可能为未来用于人类提供潜力。