| Literature DB >> 27396732 |
Bruno J Neves1, Rafael F Dantas2, Mario R Senger2, Cleber C Melo-Filho1, Walter C G Valente2, Ana C M de Almeida2, João M Rezende-Neto2, Elid F C Lima2, Ross Paveley3, Nicholas Furnham3, Eugene Muratov4, Lee Kamentsky5, Anne E Carpenter5, Rodolpho C Braga1, Floriano P Silva-Junior2, Carolina Horta Andrade1.
Abstract
Schistosomiasis is a debilitating neglected tropical disease, caused by flatworms of Schistosoma genus. The treatment relies on a single drug, praziquantel (PZQ), making the discovery of new compounds extremely urgent. In this work, we integrated QSAR-based virtual screening (VS) of Schistosoma mansoni thioredoxin glutathione reductase (SmTGR) inhibitors and high content screening (HCS) aiming to discover new antischistosomal agents. Initially, binary QSAR models for inhibition of SmTGR were developed and validated using the Organization for Economic Co-operation and Development (OECD) guidance. Using these models, we prioritized 29 compounds for further testing in two HCS platforms based on image analysis of assay plates. Among them, 2-[2-(3-methyl-4-nitro-5-isoxazolyl)vinyl]pyridine and 2-(benzylsulfonyl)-1,3-benzothiazole, two compounds representing new chemical scaffolds have activity against schistosomula and adult worms at low micromolar concentrations and therefore represent promising antischistosomal hits for further hit-to-lead optimization.Entities:
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Year: 2016 PMID： 27396732 PMCID： PMC5844225 DOI： 10.1021/acs.jmedchem.5b02038
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446