Literature DB >> 17197182

High-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity.

Derek C Martyn1, Deuan C Jones, Alan H Fairlamb, Jon Clardy.   

Abstract

Trypanothione reductase (TR), an enzyme that buffers oxidative stress in trypanosomatid parasites, was screened against commercial libraries containing approximately 134,500 compounds. After secondary screening, four chemotypes were identified as screening positives with selectivity for TR over human glutathione reductase. Thirteen compounds from these four chemotypes were purchased, and their in vitro activity against TR and Trypanosoma brucei is described.

Entities:  

Mesh：

Substances：

Year:  2006        PMID： 17197182      PMCID： PMC3428910          DOI： 10.1016/j.bmcl.2006.12.016

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


  7 in total

1.  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

2.  Ellman's-reagent-mediated regeneration of trypanothione in situ: substrate-economical microplate and time-dependent inhibition assays for trypanothione reductase.

Authors:  Chris J Hamilton; Ahilan Saravanamuthu; Ian M Eggleston; Alan H Fairlamb
Journal:  Biochem J       Date:  2003-02-01       Impact factor: 3.857

3.  The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro.

Authors:  B Räz; M Iten; Y Grether-Bühler; R Kaminsky; R Brun
Journal:  Acta Trop       Date:  1997-11       Impact factor: 3.112

4.  Substrate interactions between trypanothione reductase and N1-glutathionylspermidine disulphide at 0.28-nm resolution.

Authors:  S Bailey; K Smith; A H Fairlamb; W N Hunter
Journal:  Eur J Biochem       Date:  1993-04-01

5.  Trypanothione reductase from Leishmania donovani. Purification, characterisation and inhibition by trivalent antimonials.

Authors:  M L Cunningham; A H Fairlamb
Journal:  Eur J Biochem       Date:  1995-06-01

6.  Site-directed mutagenesis of the redox-active cysteines of Trypanosoma cruzi trypanothione reductase.

Authors:  A Borges; M L Cunningham; J Tovar; A H Fairlamb
Journal:  Eur J Biochem       Date:  1995-03-15

Review 7.  Metabolism and functions of trypanothione in the Kinetoplastida.

Authors:  A H Fairlamb; A Cerami
Journal:  Annu Rev Microbiol       Date:  1992       Impact factor: 15.500
  7 in total
  18 in total

1.  High throughput screening against the peroxidase cascade of African trypanosomes identifies antiparasitic compounds that inactivate tryparedoxin.

Authors:  Florian Fueller; Britta Jehle; Kerstin Putzker; Joe D Lewis; R Luise Krauth-Siegel
Journal:  J Biol Chem       Date:  2012-01-23       Impact factor: 5.157

2.  Antiprotozoal activity of 1-phenethyl-4-aminopiperidine derivatives.

Authors:  Christophe Dardonville; Cristina Fernández-Fernández; Sarah-Louise Gibbons; Nadine Jagerovic; Lidia Nieto; Gary Ryan; Marcel Kaiser; Reto Brun
Journal:  Antimicrob Agents Chemother       Date:  2009-06-29       Impact factor: 5.191

Review 3.  Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis.

Authors:  Advait S Nagle; Shilpi Khare; Arun Babu Kumar; Frantisek Supek; Andriy Buchynskyy; Casey J N Mathison; Naveen Kumar Chennamaneni; Nagendar Pendem; Frederick S Buckner; Michael H Gelb; Valentina Molteni
Journal:  Chem Rev       Date:  2014-11-03       Impact factor: 60.622

4.  A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity.

Authors:  Elizabeth R Sharlow; Todd A Lyda; Heidi C Dodson; Gabriela Mustata; Meredith T Morris; Stephanie S Leimgruber; Kuo-Hsiung Lee; Yoshiki Kashiwada; David Close; John S Lazo; James C Morris
Journal:  PLoS Negl Trop Dis       Date:  2010-04-13

5.  Inhibitors of tubulin assembly identified through screening a compound library.

Authors:  Rachel E Morgan; Sunnoo Ahn; Sandra Nzimiro; Jean Fotie; Mitch A Phelps; Jeffrey Cotrill; Adam J Yakovich; Dan L Sackett; James T Dalton; Karl A Werbovetz
Journal:  Chem Biol Drug Des       Date:  2008-12       Impact factor: 2.817

6.  A luciferase based viability assay for ATP detection in 384-well format for high throughput whole cell screening of Trypanosoma brucei brucei bloodstream form strain 427.

Authors:  Melissa L Sykes; Vicky M Avery
Journal:  Parasit Vectors       Date:  2009-11-12       Impact factor: 3.876

7.  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

8.  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

9.  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

10.  Improved tricyclic inhibitors of trypanothione reductase by screening and chemical synthesis.

Authors:  John L Richardson; Isabelle R E Nett; Deuan C Jones; Mohamed H Abdille; Ian H Gilbert; Alan H Fairlamb
Journal:  ChemMedChem       Date:  2009-08       Impact factor: 3.466
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.