Publications de Edina Rita Székely

6,11-Dioxobenzo[f]pyrido[1,2-a]indoles Kill Mycobacterium tuberculosis by Targeting Iron-Sulfur Protein Rv0338c (IspQ), A Putative Redox Sensor

Stewart Cole, Kai Johnsson, Andrej Benjak, Jérémie Piton, Edina Rita Székely, Monica Rengifo Gonzalez

Screening of a diversity-oriented compound library led to the identification of two 6,11-dioxobenzo[f]pyrido[1,2-a]indoles (DBPI) that displayed low micromolar bactericidal activity against the Erdman strain of Mycobacterium tuberculosis in vitro. The acti ...

AMER CHEMICAL SOC2020

Identification of aminopyrimidine-sulfonamides as potent modulators of Wag31-mediated cell elongation in mycobacteria

Stewart Cole, Kai Johnsson, John McKinney, Graham Knott, Neeraj Dhar, Ruben Hartkoorn, Isabella Santi, Anthony Vocat, Gaëlle Séraphine Kolly, Monica Rengifo Gonzalez

There is an urgent need to discover new antitubercular agents with novel mechanisms of action in order to tackle the scourge of drug-resistant tuberculosis. Here, we report the identification of such a molecule - an AminoPYrimidine-Sulfonamide (APYS1) that ...

Wiley-Blackwell2017

Mechanistic insight into mycobacterial MmpL protein function

Stewart Cole, Edina Rita Székely

Mycobacterial cell walls are complex structures containing a broad range of unusual lipids, glycolipids and other polymers, some of which act as immunomodulators or virulence determinants. Better understanding of the enzymes involved in export processes wo ...

Wiley-Blackwell2016

Development of 3,5-Dinitrobenzylsulfanyl-1,3,4-oxadiazoles and Thiadiazoles as Selective Antitubercular Agents Active Against Replicating and Nonreplicating Mycobacterium tuberculosis

Stewart Cole, Anthony Vocat, Edina Rita Székely

Herein, we report the discovery and structure activity relationships of 5-substituted-2-[(3,5-dinitrobenzyl)-sulfanyl]-1,3,4-oxadiazoles and 1,3,4-thiadiazoles as a new class of antituberculosis agents. The majority of these compounds exhibited outstanding ...

American Chemical Society2016

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

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

Anticytolytic Screen Identifies Inhibitors of Mycobacterial Virulence Protein Secretion

Stewart Cole, Claudia Sala, Ruben Hartkoorn, Andrej Benjak, Ming Zhang, Anthony Vocat, Jan Lars Rybniker, Jeffrey Chen, Edina Rita Székely

Mycobacterium tuberculosis (Mtb) requires protein secretion systems like ESX-1 for intracellular survival and virulence. The major virulence determinant and ESX-1 substrate, EsxA, arrests phagosome maturation and lyses cell membranes, resulting in tissue d ...

Cell Press2014

Leads for antitubercular compounds from kinase inhibitor library screens

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

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

A novel drug discovery concept for tuberculosis: inhibition of bacterial and host cell signalling

Stewart Cole, Edina Rita Székely, Gabor Nemeth

The Mycobacterium tuberculosis genome encodes for eleven eukaryotic-like Ser/Thr protein kinases. At least three of these (PknA, PknB and PknG) are essential for bacterial growth and survival. PknG is secreted by pathogenic mycobacteria, in macrophages to ...

2008