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

  • Giorgia Mori, Laurent R. Chiarelli, Marta Esposito, Vadim Makarov, Marco Bellinzoni, Ruben C. Hartkoorn, Giulia Degiacomi, Francesca Boldrin, Sean Ekins, Ana Luisa de Jesus Lopes Ribeiro, Leonardo B. Marino, Ivana Centárová, Zuzana Svetlíková, Jaroslav Blaško, Elena Kazakova, Alexander Lepioshkin, Nathalie Barilone, Giuseppe Zanoni, Alessio Porta, Marco Fondi, Renato Fani, Alain R. Baulard, Katarína Mikušová, Pedro M. Alzari, Riccardo Manganelli, Luiz Pedro S. de Carvalho, Giovanna Riccardi, Stewart T. Cole, Maria Rosalia Pasca
  • Chemistry & Biology, July 2015, Elsevier
  • DOI: 10.1016/j.chembiol.2015.05.016

What is it about?

Identification of compounds that are activated by EthA and then inhibit PyrG in Mtb.

Why is it important?

Integration of screening, molecular, biochemical, structural, chemistry and computational efforts lead to lead compounds. that inhibit PyrG and a crystal structure.

Perspectives

Dr Sean Ekins
Collaborations in Chemistry

My contribution to this large collaborative project was the docking and identification of additional compounds to test. THis alone was important as it suggests that compounds already screened versus Mtb may be hitting this target and they may not require EthA for activation. The work was funded by the EC FP7.

Read Publication

http://dx.doi.org/10.1016/j.chembiol.2015.05.016

The following have contributed to this page: Dr Sean Ekins