Literature DB >> 24900769

Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi Phosphofructokinase.

Kyle R Brimacombe1, Martin J Walsh1, Li Liu1, Montserrat G Vásquez-Valdivieso2, Hugh P Morgan2, Iain McNae2, Linda A Fothergill-Gilmore2, Paul A M Michels3, Douglas S Auld1, Anton Simeonov1, Malcolm D Walkinshaw2, Min Shen1, Matthew B Boxer1.   

Abstract

Human African Trypanosomiasis (HAT) is a severe, often fatal disease caused by the parasitic protist Trypanosoma brucei. The glycolytic pathway has been identified as the sole mechanism for ATP generation in the infective stage of these organisms, and several glycolytic enzymes, phosphofructokinase (PFK) in particular, have shown promise as potential drug targets. Herein, we describe the discovery of ML251, a novel nanomolar inhibitor of T. brucei PFK, and the structure-activity relationships within the series.

Entities:  

Keywords:  Trypanosoma brucei; Trypanosoma cruzi; glycolysis; high-throughput screening; inhibitors; phosphofructokinase

Year:  2013        PMID： 24900769      PMCID： PMC4027769          DOI： 10.1021/ml400259d

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  16 in total

1.  Quantitative high-throughput screening: a titration-based approach that efficiently identifies biological activities in large chemical libraries.

Authors:  James Inglese; Douglas S Auld; Ajit Jadhav; Ronald L Johnson; Anton Simeonov; Adam Yasgar; Wei Zheng; Christopher P Austin
Journal:  Proc Natl Acad Sci U S A       Date:  2006-07-24       Impact factor: 11.205

Review 2.  Compartmentation of carbohydrate metabolism in trypanosomes.

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Review 3.  A review of animal phosphofructokinase isozymes with an emphasis on their physiological role.

Authors:  G A Dunaway
Journal:  Mol Cell Biochem       Date:  1983       Impact factor: 3.396

Review 4.  Glycolysis as a target for the design of new anti-trypanosome drugs.

Authors:  C L Verlinde; V Hannaert; C Blonski; M Willson; J J Périé; L A Fothergill-Gilmore; F R Opperdoes; M H Gelb; W G Hol; P A Michels
Journal:  Drug Resist Updat       Date:  2001-02       Impact factor: 18.500

Review 5.  Chemotherapy against human African trypanosomiasis: is there a road to success?

Authors:  Christian Burri
Journal:  Parasitology       Date:  2010-10-20       Impact factor: 3.234

Review 6.  State of the art in African trypanosome drug discovery.

Authors:  Robert T Jacobs; Bakela Nare; Margaret A Phillips
Journal:  Curr Top Med Chem       Date:  2011       Impact factor: 3.295

7.  Design, synthesis and trypanocidal activity of lead compounds based on inhibitors of parasite glycolysis.

Authors:  Matthew W Nowicki; Lindsay B Tulloch; Liam Worralll; Iain W McNae; Véronique Hannaert; Paul A M Michels; Linda A Fothergill-Gilmore; Malcolm D Walkinshaw; Nicholas J Turner
Journal:  Bioorg Med Chem       Date:  2008-03-21       Impact factor: 3.641

8.  The crystal structure of ATP-bound phosphofructokinase from Trypanosoma brucei reveals conformational transitions different from those of other phosphofructokinases.

Authors:  Iain W McNae; José Martinez-Oyanedel; Jeffrey W Keillor; Paul A M Michels; Linda A Fothergill-Gilmore; Malcolm D Walkinshaw
Journal:  J Mol Biol       Date:  2008-12-03       Impact factor: 5.469

9.  Molecular and biochemical characterisation of Trypanosoma cruzi phosphofructokinase.

Authors:  Evelyn Rodríguez; Noelia Lander; Jose Luis Ramirez
Journal:  Mem Inst Oswaldo Cruz       Date:  2009-08       Impact factor: 2.743

Review 10.  The trypanosomiases.

Authors:  Michael P Barrett; Richard J S Burchmore; August Stich; Julio O Lazzari; Alberto Carlos Frasch; Juan José Cazzulo; Sanjeev Krishna
Journal:  Lancet       Date:  2003-11-01       Impact factor: 79.321
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  9 in total

Review 1.  Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future.

Authors:  Wim G J Hol
Journal:  Acta Crystallogr F Struct Biol Commun       Date:  2015-04-16       Impact factor: 1.056

Review 2.  Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need.

Authors:  Mark C Field; David Horn; Alan H Fairlamb; Michael A J Ferguson; David W Gray; Kevin D Read; Manu De Rycker; Leah S Torrie; Paul G Wyatt; Susan Wyllie; Ian H Gilbert
Journal:  Nat Rev Microbiol       Date:  2017-02-27       Impact factor: 60.633

3.  The kinetic characteristics of human and trypanosomatid phosphofructokinases for the reverse reaction.

Authors:  Peter M Fernandes; James Kinkead; Iain W McNae; Frédéric Bringaud; Paul A M Michels; Malcolm D Walkinshaw
Journal:  Biochem J       Date:  2019-01-18       Impact factor: 3.857

4.  Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice.

Authors:  Iain W McNae; James Kinkead; Divya Malik; Li-Hsuan Yen; Martin K Walker; Chris Swain; Scott P Webster; Nick Gray; Peter M Fernandes; Elmarie Myburgh; Elizabeth A Blackburn; Ryan Ritchie; Carol Austin; Martin A Wear; Adrian J Highton; Andrew J Keats; Antonio Vong; Jacqueline Dornan; Jeremy C Mottram; Paul A M Michels; Simon Pettit; Malcolm D Walkinshaw
Journal:  Nat Commun       Date:  2021-02-16       Impact factor: 14.919

Review 5.  Structure, function and druggability of the African trypanosome flagellum.

Authors:  Julia Sáez Conde; Samuel Dean
Journal:  J Cell Physiol       Date:  2022-05-26       Impact factor: 6.513

6.  Partially Purified Leaf Fractions of Azadirachta indica Inhibit Trypanosome Alternative Oxidase and Exert Antitrypanosomal Effects on Trypanosoma congolense.

Authors:  Abdullah M Tauheed; Mohammed Mamman; Abubakar Ahmed; Mohammed M Suleiman; Emmanuel O Balogun
Journal:  Acta Parasitol       Date:  2021-06-22       Impact factor: 1.534

Review 7.  Kinases as druggable targets in trypanosomatid protozoan parasites.

Authors:  Christopher Merritt; Lisseth E Silva; Angela L Tanner; Kenneth Stuart; Michael P Pollastri
Journal:  Chem Rev       Date:  2014-10-07       Impact factor: 60.622

8.  Kinetic and structural studies of Trypanosoma and Leishmania phosphofructokinases show evolutionary divergence and identify AMP as a switch regulating glycolysis versus gluconeogenesis.

Authors:  Peter M Fernandes; James Kinkead; Iain W McNae; Monserrat Vásquez-Valdivieso; Martin A Wear; Paul A M Michels; Malcolm D Walkinshaw
Journal:  FEBS J       Date:  2020-01-08       Impact factor: 5.542

9.  Digalloyl Glycoside: A Potential Inhibitor of Trypanosomal PFK from Euphorbia abyssinica J.F. Gmel.

Authors:  Seham S El-Hawary; Rabab Mohammed; Nadia M Lithy; Sameh Fekry AbouZid; Mostafa A Mansour; Suliman A Almahmoud; Bader Huwaimel; Elham Amin
Journal:  Plants (Basel)       Date:  2022-01-10
  9 in total

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