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Ruben Hartkoorn

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Related publications (30)

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Thiophenecarboxamide Derivatives Activated by EthA Kill Mycobacterium tuberculosis by Inhibiting the CTP Synthetase PyrG

Stewart Cole, Ruben Hartkoorn

To combat the emergence of drug-resistant strains of Mycobacterium tuberculosis, new antitubercular agents and novel drug targets are needed. Phenotypic screening of a library of 594 hit compounds uncovered two leads that were active against M. tuberculosi ...

Elsevier2015

A Simple Model for Testing Drugs against Non-replicating Mycobacterium tuberculosis

Stewart Cole, Neeraj Dhar, Claudia Sala, Ruben Hartkoorn, Ming Zhang

Non-replicating or dormant cells of Mycobacterium tuberculosis constitute a challenge to tuberculosis (TB) therapy because of their tolerance or phenotypic resistance to most drugs. Here, we propose a simple model for testing drugs against non-growing cell ...

2010

Micrococcin P1-A bactericidal thiopeptide active against Mycobacterium tuberculosis

Stewart Cole, Andrej Benjak, Ruben Hartkoorn

The lack of proper treatment for serious infectious diseases due to the emergence of multidrug resistance reinforces the need for the discovery of novel antibiotics. This is particularly true for tuberculosis (TB) for which 3.7% of new cases and 20% of pre ...

Elsevier2016

Streptomycin-Starved Mycobacterium tuberculosis 18b, a Drug Discovery Tool for Latent Tuberculosis

Stewart Cole, Claudia Sala, Neeraj Dhar, Ruben Hartkoorn, Ming Zhang

Mycobacterium tuberculosis 18b, a streptomycin (STR)-dependent mutant that enters a viable but nonreplicating state in the absence of STR, has been developed as a simple model for drug testing against dormant bacilli. Here, we further evaluated the STR-sta ...

Amer Soc Microbiology2012

The Inosine Monophosphate Dehydrogenase, GuaB2, Is a Vulnerable New Bactericidal Drug Target for Tuberculosis

Stewart Cole, John McKinney, Claudia Sala, Neeraj Dhar, Anthony Vocat, Ruben Hartkoorn, Andréanne Lupien, Raphael Christopher Sommer

VCC234718, a molecule with growth inhibitory activity against Mycobacterium tuberculosis (Mtb), was identified by phenotypic screening of a 15344-compound library. Sequencing of a VCC234718-resistant mutant identified a Y487C substitution in the inosine mo ...

Amer Chemical Soc2017

2-Carboxyquinoxalines Kill Mycobacterium tuberculosis through Noncovalent Inhibition of DprE1

Stewart Cole, Neeraj Dhar, Florence Pojer, Ruben Hartkoorn, Gaëlle Séraphine Kolly, Joao Pedro De Almeida Neres

Phenotypic screening of a quinoxaline library against replicating Mycobacterium tuberculosis led to the identification of lead compound Ty38c (3-((4-methoxybenzyl)amino)-6-(trifluoromethyl)quinoxaline-2-carboxylic acid). With an MIC99 and MBC of 3.1 mu M, ...

American Chemical Society2015

Whole cell screen based identification of spiropiperidines with potent antitubercular properties

Stewart Cole, Ruben Hartkoorn

Whole cell based screens to identify hits against Mycobacterium tuberculosis (Mtb), carried out under replicating and non-replicating (NRP) conditions, resulted in the identification of multiple, novel but structurally related spiropiperidines with potent ...

Elsevier2015

Genome-Wide Definition of the SigF Regulon in Mycobacterium tuberculosis

Stewart Cole, Jacques Rougemont, Claudia Sala, Ruben Hartkoorn, Philippe Busso, Swapna Uplekar

In Mycobacterium tuberculosis the alternative sigma factor SigF controls the expression of a particular subset of genes by altering RNA polymerase specificity. Here, we utilize two genome-wide approaches to identify SigF-binding sites: chromatin immunoprec ...

American Society for Microbiology2012

Synthesis and Structure-Activity Relationship Studies of C2-Modified Analogs of the Antimycobacterial Natural Product Pyridomycin

Stewart Cole, Ruben Hartkoorn, Anthony Vocat

A series of derivatives of the antimycobacterial natural product pyridomycin have been prepared with the C2 side chain attached to the macrocyclic core structure by a C-C single bond, in place of the synthetically more demanding enol ester double bond foun ...

AMER CHEMICAL SOC2020

Lead selection and characterization of antitubercular compounds using the Nested Chemical Library

Stewart Cole, Ruben Hartkoorn, Edina Rita Székely

Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find novel antitubercular agents several approaches have been used in various institutions worldwide, including target-based ap ...

Elsevier2015

Discovery and Biosynthesis of Gladiolin: A Burkholderia gladioli Antibiotic with Promising Activity against Mycobacterium tuberculosis

Stewart Cole, Anthony Vocat, Ruben Hartkoorn

An antimicrobial activity screen of Burkholderia gladioli BCC0238, a clinical isolate from a cystic fibrosis patient, led to the discovery of gladiolin, a novel macrolide antibiotic with potent activity against Mycobacterium tuberculosis H37Rv. Gladiolin i ...

Amer Chemical Soc2017

Virulence Regulator EspR of Mycobacterium tuberculosis Is a Nucleoid-Associated Protein

Stewart Cole, Jacques Rougemont, Claudia Sala, Florence Pojer, Ruben Hartkoorn, Swapna Uplekar, Benjamin Blasco

The principal virulence determinant of Mycobacterium tuberculosis (Mtb), the ESX-1 protein secretion system, is positively controlled at the transcriptional level by EspR. Depletion of EspR reportedly affects a small number of genes, both positively or neg ...

Public Library of Science2012

Tuberculosis drugs: new candidates and how to find more

Claudia Sala, Ruben Hartkoorn

The recent years have witnessed significant progress in the development of new drug candidates for the treatment of TB. While many of these are now in clinical trials, continued research is needed in order to sustain the drug discovery pipeline and meet th ...

2011

Sigma Factor F does not Prevent Rifampin Inhibition of RNA Polymerase or Cause Rifampin Tolerance in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Florence Pojer, Ruben Hartkoorn, Sophie Magnet

The tolerance of Mycobacterium tuberculosis to anti-tuberculosis drugs is a major reason for the lengthy therapy needed to treat a tuberculosis infection. Rifampin is a potent inhibitor of RNA polymerase (RNAP) in vivo, but has been shown to be less effect ...

American Society for Microbiology2010

Towards a new tuberculosis drug: pyridomycin - nature's isoniazid

Stewart Cole, Claudia Sala, Florence Pojer, Ruben Hartkoorn, Swapna Uplekar, Joao Pedro De Almeida Neres, Raju Mukherjee, Sophie Magnet

Tuberculosis, a global threat to public health, is becoming untreatable due to widespread drug resistance to frontline drugs such as the InhA-inhibitor isoniazid. Historically, by inhibiting highly vulnerable targets, natural products have been an importan ...

Wiley Open Access2012

4-Pyrimidinylamino-benzenesulfonamide derivatives and their use for the inhibition of polo-like kinase 1 (PLK1) for the treatment of cancer and their use for the treatment of bacterial infections

Stewart Cole, Ruben Hartkoorn, Edina Rita Székely

The present invention relates to 4-pyrimidinylamino-benzenesulfonamide derivatives of general formula (I) and pharmaceutically acceptable salts, solvates, hydrates, regioisomeric and polymorphic forms thereof, processes for manufacturing of them, the use o ...

2015

Intracellular 'boosting' of darunavir using known transport inhibitors in primary PBMC

Ruben Hartkoorn

center dot Antiretroviral protease inhibitors such as lopinavir and saquinavir have been shown to be substrates of ABCB1. Co-administration with the potent ABCB1 and CYP3A4 inhibitor, ritonavir, has shown improved pharmacokinetics and subsequent therapeuti ...

2009

Leads for antitubercular compounds from kinase inhibitor library screens

Stewart Cole, Gerardo Turcatti, Ruben Hartkoorn, Marc Chambon, Damiano Banfi, Edina Rita Székely, Sophie Magnet

Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find antimycobacterial scaffolds, we screened a kinase inhibitor library of more than 12,000 compounds using an integrated stra ...

2010

In Vitro Combination Studies of Benzothiazinone Lead Compound BTZ043 against Mycobacterium tuberculosis

Stewart Cole, Ruben Hartkoorn, Benoit Lechartier

Benzothiazinones (BTZ) are a new class of drug candidates to combat tuberculosis that inhibit decaprenyl-phosphoribose epimerase (DprE1), an essential enzyme involved in arabinan biosynthesis. Using the checkerboard method and cell viability assays, we hav ...

Amer Soc Microbiology2012

The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis

Stewart Cole, Anthony Vocat, Ruben Hartkoorn, Jérémie Piton, Gaëlle Séraphine Kolly, Joao Pedro De Almeida Neres, Trent Michael Conroy

8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-beta-D-ribose 2'-oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. Structure-activity relationship (SAR) studie ...

American Society for Microbiology2015