Discovery of novel drug-like antitubercular hits targeting the MEP pathway enzyme DXPS by strategic application of ligand-based virtual screening-Reference-Cited by-同舟云学术

Discovery of novel drug-like antitubercular hits targeting the MEP pathway enzyme DXPS by strategic application of ligand-based virtual screening

Published:2022 Issue:36 Volume:13 Page:10686-10698
ISSN:2041-6520
Container-title:Chemical Science
language:en
Short-container-title:Chem. Sci.

Author:

Zhu Di¹²³,Johannsen Sandra¹²^ORCID,Masini Tiziana³,Simonin Céline⁴,Haupenthal Jörg¹,Illarionov Boris⁵,Andreas Anastasia¹²,Awale Mahendra⁴,Gierse Robin M.¹²³^ORCID,van der Laan Tridia⁶,van der Vlag Ramon³^ORCID,Nasti Rita³,Poizat Mael⁷,Buhler Eric⁸^ORCID,Reiling Norbert⁹¹⁰,Müller Rolf¹²¹¹^ORCID,Fischer Markus⁵^ORCID,Reymond Jean-Louis⁴,Hirsch Anna K. H.¹²³¹¹^ORCID

Affiliation:

1. Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) – Helmholtz Centre for Infection Research (HZI), Campus Building E8.1, 66123 Saarbrücken, Germany

2. Department of Pharmacy, Saarland University, Campus Building E8.1, 66123 Saarbrücken, Germany

3. Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands

4. Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland

5. Hamburg School of Food Science, Institute of Food Chemistry, Grindelallee 117, 20146 Hamburg, Germany

6. Department of Mycobacteria, National Institute of Public Health and the Environment (RIVM), Diagnostics and Laboratory Surveillance (IDS), Infectious Diseases Research, Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands

7. Symeres, Kadijk 3, 9747 AT Groningen, The Netherlands

8. Laboratoire Matière et Systèmes Complexes (MSC), UMR CNRS 7057, Université Paris Cité, Bâtiment Condorcet, 75205 Paris Cedex 13, France

9. RG Microbial Interface Biology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany

10. German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany

11. Helmholtz International Lab for Anti-infectives, Campus Building E8.1, 66123 Saarbrücken, Germany

Abstract

We identified two drug-like antitubercular hits with submicromolar inhibition constants against the target 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) with a new mode of action and promising activity against drug-resistant tuberculosis.

Funder

H2020 European Research Council

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Publisher

Royal Society of Chemistry (RSC)

Subject

General Chemistry

Link

http://pubs.rsc.org/en/content/articlepdf/2022/SC/D2SC02371G

Reference61 articles.

1. The Science of Antibiotic Discovery

2. Druggability and drug-likeness concepts in drug design: are biomodelling and predictive tools having their say?