High Throughput Screening Identifies Novel Lead Compounds with Activity against Larval, Juvenile and Adult Schistosoma mansoni

被引：34

作者：

Mansour, Nuha R. ^{[1
]}

Paveley, Ross ^{[1
]}

Gardner, J. Mark F. ^{[2
]}

Bell, Andrew S. ^{[2
]}

Parkinson, Tanya ^{[2
]}

Bickle, Quentin ^{[1
]}

机构：

[1] London Sch Hyg & Trop Med, Dept Infect Immunol, London WC1, England

[2] Salvensis, Discovery Pk House,Discovery Pk, Sandwich, Kent, England

来源：

PLOS NEGLECTED TROPICAL DISEASES | 2016年 / 10卷 / 04期

基金：

英国医学研究理事会;

关键词：

DRUG DISCOVERY; PRAZIQUANTEL; ASSAY; STRATEGIES; INHIBITORS; LIBRARY; HIT;

D O I：

10.1371/journal.pntd.0004659

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

An estimated 600 million people are affected by the helminth disease schistosomiasis caused by parasites of the genus Schistosoma. There is currently only one drug recommended for treating schistosomiasis, praziquantel (PZQ), which is effective against adult worms but not against the juvenile stage. In an attempt to identify improved drugs for treating the disease, we have carried out high throughput screening of a number of small molecule libraries with the aim of identifying lead compounds with balanced activity against all life stages of Schistosoma. A total of almost 300,000 compounds were screened using a high throughput assay based on motility of worm larvae and image analysis of assay plates. Hits were screened against juvenile and adult worms to identify broadly active compounds and against a mammalian cell line to assess cytotoxicity. A number of compounds were identified as promising leads for further chemical optimization.

引用

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