Literature DB >> 34280206

The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species.

J Mark F Gardner1, Nuha R Mansour2, Andrew S Bell1, Helena Helmby2, Quentin Bickle2.   

Abstract

Treatment and control of schistosomiasis depends on a single drug, praziquantel, but this is not ideal for several reasons including lack of potency against the juvenile stage of the parasite, dose size, and risk of resistance. We have optimised the properties of a series of compounds we discovered through high throughput screening and have designed candidates for clinical development. The best compounds demonstrate clearance of both juvenile and adult S. mansoni worms in a mouse model of infection from a single oral dose of < 10 mg/kg. Several compounds in the series are predicted to treat schistosomiasis in humans across a range of species with a single oral dose of less than 5 mg/kg.

Entities:  

Year:  2021        PMID: 34280206     DOI: 10.1371/journal.pntd.0009490

Source DB:  PubMed          Journal:  PLoS Negl Trop Dis        ISSN: 1935-2727


  26 in total

1.  Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment.

Authors:  Livia Pica-Mattoccia; Donato Cioli
Journal:  Int J Parasitol       Date:  2004-03-29       Impact factor: 3.981

2.  How has the genomics era impacted schistosomiasis drug discovery?

Authors:  Guilherme Oliveira; Raymond J Pierce
Journal:  Future Med Chem       Date:  2015       Impact factor: 3.808

3.  Schistosoma mansoni: chemotherapy of infections of different ages.

Authors:  A A Sabah; C Fletcher; G Webbe; M J Doenhoff
Journal:  Exp Parasitol       Date:  1986-06       Impact factor: 2.011

Review 4.  Chemotherapy for human schistosomiasis: how far have we come? What's new? Where do we go from here?

Authors:  Godwin Akpeko Dziwornu; Henrietta Dede Attram; Samuel Gachuhi; Kelly Chibale
Journal:  RSC Med Chem       Date:  2020-04-06

Review 5.  Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis.

Authors:  Michael J Doenhoff; Donato Cioli; Jürg Utzinger
Journal:  Curr Opin Infect Dis       Date:  2008-12       Impact factor: 4.915

6.  The Mechanism of Action of Praziquantel: Can New Drugs Exploit Similar Mechanisms?

Authors:  Charlotte M Thomas; David J Timson
Journal:  Curr Med Chem       Date:  2020       Impact factor: 4.530

7.  Alternatives to Praziquantel for the Prevention and Control of Schistosomiasis.

Authors:  Thomas Spangenberg
Journal:  ACS Infect Dis       Date:  2020-08-21       Impact factor: 5.084

Review 8.  The unacknowledged impact of chronic schistosomiasis.

Authors:  Charles H King; Madeline Dangerfield-Cha
Journal:  Chronic Illn       Date:  2008-03

9.  Expanding the Activity Profile of Pyrido[1,2-a]benzimidazoles: Synthesis and Evaluation of Novel N1-1-Phenylethanamine Derivatives against Schistosoma mansoni.

Authors:  Alexandra Probst; Kelly Chisanga; Godwin Akpeko Dziwornu; Cécile Haeberli; Jennifer Keiser; Kelly Chibale
Journal:  ACS Infect Dis       Date:  2020-08-18       Impact factor: 5.084

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

Authors:  Nuha R Mansour; Ross Paveley; J Mark F Gardner; Andrew S Bell; Tanya Parkinson; Quentin Bickle
Journal:  PLoS Negl Trop Dis       Date:  2016-04-29
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  1 in total

1.  Identification of novel modulators of a schistosome transient receptor potential channel targeted by praziquantel.

Authors:  Evgeny G Chulkov; Emery Smith; Claudia M Rohr; Nawal A Yahya; Sang-Kyu Park; Louis Scampavia; Timothy P Spicer; Jonathan S Marchant
Journal:  PLoS Negl Trop Dis       Date:  2021-11-03
  1 in total

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