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Literature DB >> 17194585

Discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase inhibitor by high-throughput screening.

Georgina A Holloway¹, Jonathan B Baell, Alan H Fairlamb, Patrizia M Novello, John P Parisot, John Richardson, Keith G Watson, Ian P Street.

Abstract

A high-throughput screening campaign of a library of 100,000 lead-like compounds identified 2-iminobenzimidazoles as a novel class of trypanothione reductase inhibitors. These 2-iminobenzimidazoles display potent trypanocidal activity against Trypanosoma brucei rhodesiense, do not inhibit closely related human glutathione reductase and have low cytotoxicity against mammalian cells.

Entities: CellLine Chemical Disease Gene Species

Mesh：

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Year: 2006 PMID： 17194585 PMCID： PMC3428904 DOI： 10.1016/j.bmcl.2006.11.090

Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823

24 in total

1. A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays.

Authors:
Journal: J Biomol Screen Date: 1999

2. Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress.

Authors: S Krieger; W Schwarz; M R Ariyanayagam; A H Fairlamb; R L Krauth-Siegel; C Clayton
Journal: Mol Microbiol Date: 2000-02 Impact factor: 3.501

3. Aromatic amination/imination approach to chiral benzimidazoles.

Authors: Felix M Rivas; Anthony J Giessert; Steven T Diver
Journal: J Org Chem Date: 2002-03-08 Impact factor: 4.354

4. Rational design of selective ligands for trypanothione reductase from Trypanosoma cruzi. Structural effects on the inhibition by dibenzazepines based on imipramine.

Authors: J Garforth; H Yin; J H McKie; K T Douglas; A H Fairlamb
Journal: J Enzyme Inhib Date: 1997-08

Review 5. Drug resistance in leishmaniasis.

Authors: Simon L Croft; Shyam Sundar; Alan H Fairlamb
Journal: Clin Microbiol Rev Date: 2006-01 Impact factor: 26.132

6. Antitrypanosomal, antileishmanial, and antimalarial activities of quaternary arylalkylammonium 2-amino-4-chlorophenyl phenyl sulfides, a new class of trypanothione reductase inhibitor, and of N-acyl derivatives of 2-amino-4-chlorophenyl phenyl sulfide.

Authors: Seheli Parveen; Mohammed O F Khan; Susan E Austin; Simon L Croft; Vanessa Yardley; Peter Rock; Kenneth T Douglas
Journal: J Med Chem Date: 2005-12-15 Impact factor: 7.446

7. Substrate specificity of trypanothione reductase.

Authors: I R Marsh; M Bradley
Journal: Eur J Biochem Date: 1997-02-01

8. Novel alkylpolyaminoguanidines and alkylpolyaminobiguanides with potent antitrypanosomal activity.

Authors: Xiangdong Bi; Christina Lopez; Cyrus J Bacchi; Donna Rattendi; Patrick M Woster
Journal: Bioorg Med Chem Lett Date: 2006-04-17 Impact factor: 2.823

9. Evidence that trypanothione reductase is an essential enzyme in Leishmania by targeted replacement of the tryA gene locus.

Authors: J Tovar; S Wilkinson; J C Mottram; A H Fairlamb
Journal: Mol Microbiol Date: 1998-07 Impact factor: 3.501

10. Synthesis and hypolipidemic activity of 2-substituted isobutyric acid derivatives.

Authors: S Morishita; T Saito; Y Hirai; M Shoji; Y Mishima; M Kawakami
Journal: J Med Chem Date: 1988-06 Impact factor: 7.446

12 in total

1. Trypanothione reductase high-throughput screening campaign identifies novel classes of inhibitors with antiparasitic activity.

Authors: Georgina A Holloway; William N Charman; Alan H Fairlamb; Reto Brun; Marcel Kaiser; Edmund Kostewicz; Patrizia M Novello; John P Parisot; John Richardson; Ian P Street; Keith G Watson; Jonathan B Baell
Journal: Antimicrob Agents Chemother Date: 2009-04-13 Impact factor: 5.191

2. Inhibitors of Leishmania GDP-mannose pyrophosphorylase identified by high-throughput screening of small-molecule chemical library.

Authors: Kurt Lackovic; John P Parisot; Nerida Sleebs; Jonathan B Baell; Laurent Debien; Keith G Watson; Joan M Curtis; Emanuela Handman; Ian P Street; Lukasz Kedzierski
Journal: Antimicrob Agents Chemother Date: 2010-02-16 Impact factor: 5.191

3. Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: discovery, synthesis, and characterization of their binding mode by protein crystallography.

Authors: Stephen Patterson; Magnus S Alphey; Deuan C Jones; Emma J Shanks; Ian P Street; Julie A Frearson; Paul G Wyatt; Ian H Gilbert; Alan H Fairlamb
Journal: J Med Chem Date: 2011-09-01 Impact factor: 7.446

4. Advancing drug innovation for neglected diseases-criteria for lead progression.

Authors: Solomon Nwaka; Bernadette Ramirez; Reto Brun; Louis Maes; Frank Douglas; Robert Ridley
Journal: PLoS Negl Trop Dis Date: 2009-08-25

5. Comparative structural, kinetic and inhibitor studies of Trypanosoma brucei trypanothione reductase with T. cruzi.

Authors: Deuan C Jones; Antonio Ariza; Wing-Huen A Chow; Sandra L Oza; Alan H Fairlamb
Journal: Mol Biochem Parasitol Date: 2009-09-10 Impact factor: 1.759

6. Investigation of trypanothione reductase as a drug target in Trypanosoma brucei.

Authors: Daniel Spinks; Emma J Shanks; Laura A T Cleghorn; Stuart McElroy; Deuan Jones; Daniel James; Alan H Fairlamb; Julie A Frearson; Paul G Wyatt; Ian H Gilbert
Journal: ChemMedChem Date: 2009-12 Impact factor: 3.466

7. Synthesis and evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) analogues as inhibitors of trypanothione reductase.

Authors: Stephen Patterson; Deuan C Jones; Emma J Shanks; Julie A Frearson; Ian H Gilbert; Paul G Wyatt; Alan H Fairlamb
Journal: ChemMedChem Date: 2009-08 Impact factor: 3.466