4.6 Article

Three Small Molecule Entities (MPK18, MPK334 and YAK308) with Activity against Haemonchus contortus In Vitro

期刊

MOLECULES
卷 26, 期 9, 页码 -

出版社

MDPI
DOI: 10.3390/molecules26092819

关键词

Haemonchus contortus; phenotypic screening; anthelmintics; small molecules

资金

  1. Australian Research Council (ARC)
  2. German Research Foundation (DFG) Research Training Group GRK 2158 [270650915]
  3. Yourgene Health Singapore Pte Ltd.

向作者/读者索取更多资源

Due to widespread multi-drug resistance in parasitic nematodes of livestock animals, there is an urgent need to discover new anthelmintics with distinct mechanisms of action. Screening of 245 chemically-diverse small molecules revealed three compounds (MPK18, MPK334, and YAK308) that showed nematocidal activity against Haemonchus contortus, inhibiting larval motility and development without toxicity to human liver cells. Further evaluation and optimization of these compounds may lead to novel anthelmintic candidates.
Due to widespread multi-drug resistance in parasitic nematodes of livestock animals, there is an urgent need to discover new anthelmintics with distinct mechanisms of action. Extending previous work, here we screened a panel of 245 chemically-diverse small molecules for anti-parasitic activity against Haemonchus contortus-an economically important parasitic nematode of livestock. This panel was screened in vitro against exsheathed third-stage larvae (xL3) of H. contortus using an established phenotypic assay, and the potency of select compounds to inhibit larval motility and development assessed in dose-response assays. Of the 245 compounds screened, three-designated MPK18, MPK334 and YAK308-induced non-wildtype larval phenotypes and repeatedly inhibited xL3-motility, with IC50 values of 45.2 mu M, 17.1 mu M and 52.7 mu M, respectively; two also inhibited larval development, with IC50 values of 12.3 mu M (MPK334) and 6.5 mu M (YAK308), and none of the three was toxic to human liver cells (HepG2). These findings suggest that these compounds deserve further evaluation as nematocidal candidates. Future work should focus on structure-activity relationship (SAR) studies of these chemical scaffolds, and assess the in vitro and in vivo efficacies and safety of optimised compounds against adults of H. contortus.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据