Skip to Main content Skip to Navigation
Journal articles

Original Chemical Series of Pyrimidine Biosynthesis Inhibitors That Boost the Antiviral Interferon Response

Abstract : De novo pyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1H-indol-3-yl)-2,3-dihydro-4H-furo[3,2-c]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit broad-spectrum antiviral activity and immunostimulatory properties, in line with recent reports linking de novo pyrimidine biosynthesis with innate defense mechanisms against viruses. Most importantly, we establish that pyrimidine deprivation can amplify the production of both type I and type III interferons by cells stimulated with retinoic acid-inducible gene 1 (RIG-I) ligands. Altogether, our results further expand the current panel of pyrimidine biosynthesis inhibitors and illustrate how the production of antiviral interferons is tightly coupled to this metabolic pathway. Functional and structural similarities between this new chemical series and dicoumarol, which was reported before to inhibit pyrimidine biosynthesis at the dihydroorotate dehydrogenase (DHODH) step, are discussed.
Document type :
Journal articles
Complete list of metadatas

Cited literature [35 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-01693518
Contributor : Hélène Munier-Lehmann <>
Submitted on : Friday, January 26, 2018 - 11:48:08 AM
Last modification on : Tuesday, July 21, 2020 - 3:59:14 AM
Long-term archiving on: : Friday, May 25, 2018 - 4:56:49 AM

File

Antimicrob. Agents Chemother.-...
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

Marianne Lucas-Hourani, Daniel Dauzonne, Hélène Munier-Lehmann, Samira Khiar, Sébastien Nisole, et al.. Original Chemical Series of Pyrimidine Biosynthesis Inhibitors That Boost the Antiviral Interferon Response. Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2017, 61 (10), pp.e00383-17. ⟨10.1128/AAC.00383-17⟩. ⟨pasteur-01693518⟩

Share

Metrics

Record views

661

Files downloads

1044