Literature DB >> 29969537

Brain-Penetrant Triazolopyrimidine and Phenylpyrimidine Microtubule Stabilizers as Potential Leads to Treat Human African Trypanosomiasis.

Ludovica Monti1, Steven C Wang1, Killian Oukoloff1, Amos B Smith2, Kurt R Brunden3, Conor R Caffrey1, Carlo Ballatore1.   

Abstract

In vitro whole-organism screens of Trypanosoma brucei with representative examples of brain-penetrant microtubule (MT)-stabilizing agents identified lethal triazolopyrimidines and phenylpyrimidines with sub-micromolar potency. In mammalian cells, these antiproliferative compounds disrupt MT integrity and decrease total tubulin levels. Their parasiticidal potency, combined with their generally favorable pharmacokinetic properties, which include oral bioavailability and brain penetration, suggest that these compounds are potential leads against human African trypanosomiasis.
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Entities:  

Keywords:  Trypanosoma brucei; human African trypanosomiasis; microtubules; phenylpyrimidines; triazolopyrimidines

Mesh：

Substances：

Year:  2018        PMID： 29969537      PMCID： PMC6286711          DOI： 10.1002/cmdc.201800404

Source DB:  PubMed          Journal:  ChemMedChem        ISSN： 1860-7179            Impact factor:   3.466


  32 in total

Review 1.  Tubulin as an antiprotozoal drug target.

Authors:  Karl A Werbovetz
Journal:  Mini Rev Med Chem       Date:  2002-12       Impact factor: 3.862

Review 2.  Human African trypanosomiasis of the CNS: current issues and challenges.

Authors:  Peter G E Kennedy
Journal:  J Clin Invest       Date:  2004-02       Impact factor: 14.808

3.  Synthesis and SAR of [1,2,4]triazolo[1,5-a]pyrimidines, a class of anticancer agents with a unique mechanism of tubulin inhibition.

Authors:  Nan Zhang; Semiramis Ayral-Kaloustian; Thai Nguyen; Jay Afragola; Richard Hernandez; Judy Lucas; James Gibbons; Carl Beyer
Journal:  J Med Chem       Date:  2007-01-25       Impact factor: 7.446

4.  Microtubules as antiparasitic drug targets.

Authors:  Bj Fennell; Ja Naughton; J Barlow; G Brennan; I Fairweather; E Hoey; N McFerran; A Trudgett; A Bell
Journal:  Expert Opin Drug Discov       Date:  2008-05       Impact factor: 6.098

5.  MT-Stabilizer, Dictyostatin, Exhibits Prolonged Brain Retention and Activity: Potential Therapeutic Implications.

Authors:  Kurt R Brunden; Nicola M Gardner; Michael J James; Yuemang Yao; John Q Trojanowski; Virginia M-Y Lee; Ian Paterson; Carlo Ballatore; Amos B Smith
Journal:  ACS Med Chem Lett       Date:  2013-07-23       Impact factor: 4.345

6.  Drug discovery for human African trypanosomiasis: identification of novel scaffolds by the newly developed HTS SYBR Green assay for Trypanosoma brucei.

Authors:  Joana Faria; Carolina B Moraes; Rita Song; Bruno S Pascoalino; Nakyung Lee; Jair L Siqueira-Neto; Deu John M Cruz; Tanya Parkinson; Jean-Robert Ioset; Anabela Cordeiro-da-Silva; Lucio H Freitas-Junior
Journal:  J Biomol Screen       Date:  2014-10-23

7.  Risk factors for treatment failure after melarsoprol for Trypanosoma brucei gambiense trypanosomiasis in Uganda.

Authors:  D Legros; S Evans; F Maiso; J C Enyaru; D Mbulamberi
Journal:  Trans R Soc Trop Med Hyg       Date:  1999 Jul-Aug       Impact factor: 2.184

8.  Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial.

Authors:  Victor Kande Betu Ku Mesu; Wilfried Mutombo Kalonji; Clélia Bardonneau; Olaf Valverde Mordt; Séverine Blesson; François Simon; Sophie Delhomme; Sonja Bernhard; Willy Kuziena; Jean-Pierre Fina Lubaki; Steven Lumeya Vuvu; Pathou Nganzobo Ngima; Hélène Mahenzi Mbembo; Médard Ilunga; Augustin Kasongo Bonama; Josué Amici Heradi; Jean Louis Lumaliza Solomo; Guylain Mandula; Lewis Kaninda Badibabi; Francis Regongbenga Dama; Papy Kavunga Lukula; Digas Ngolo Tete; Crispin Lumbala; Bruno Scherrer; Nathalie Strub-Wourgaft; Antoine Tarral
Journal:  Lancet       Date:  2017-11-04       Impact factor: 79.321

9.  Design, synthesis and evaluation of photoactivatable derivatives of microtubule (MT)-active [1,2,4]triazolo[1,5-a]pyrimidines.

Authors:  Killian Oukoloff; Jane Kovalevich; Anne-Sophie Cornec; Yuemang Yao; Zachary A Owyang; Michael James; John Q Trojanowski; Virginia M-Y Lee; Amos B Smith; Kurt R Brunden; Carlo Ballatore
Journal:  Bioorg Med Chem Lett       Date:  2018-05-05       Impact factor: 2.823

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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  3 in total

Review 1.  1,2,4-Triazolo[1,5-a]pyrimidines in drug design.

Authors:  Killian Oukoloff; Bobby Lucero; Karol R Francisco; Kurt R Brunden; Carlo Ballatore
Journal:  Eur J Med Chem       Date:  2019-01-14       Impact factor: 6.514

2.  Congeners Derived from Microtubule-Active Phenylpyrimidines Produce a Potent and Long-Lasting Paralysis of Schistosoma mansoni In Vitro.

Authors:  Ludovica Monti; Anne-Sophie Cornec; Killian Oukoloff; Jane Kovalevich; Kristen Prijs; Thibault Alle; Kurt R Brunden; Amos B Smith; Nelly El-Sakkary; Lawrence J Liu; Ali Syed; Danielle E Skinner; Carlo Ballatore; Conor R Caffrey
Journal:  ACS Infect Dis       Date:  2020-10-31       Impact factor: 5.084

3.  Identification of anisomycin, prodigiosin and obatoclax as compounds with broad-spectrum anti-parasitic activity.

Authors:  Gretchen Ehrenkaufer; Pengyang Li; Erin E Stebbins; Monica M Kangussu-Marcolino; Anjan Debnath; Corin V White; Matthew S Moser; Joseph DeRisi; Jolyn Gisselberg; Ellen Yeh; Steven C Wang; Ana Hervella Company; Ludovica Monti; Conor R Caffrey; Christopher D Huston; Bo Wang; Upinder Singh
Journal:  PLoS Negl Trop Dis       Date:  2020-03-20
  3 in total

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