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© Research
Publication : Journal of medicinal chemistry

Design, Synthesis, and Efficacy Testing of Nitroethylene- and 7-Nitrobenzoxadiazol-Based Flavodoxin Inhibitors against Drug-Resistant Clinical Strains and in Infected Mice

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of medicinal chemistry - 21 Jun 2019

Salillas S, Alías M, Michel V, Mahía A, Lucía A, Rodrigues L, Bueno J, Galano-Frutos JJ, De Reuse H, Velázquez-Campoy A, Carrodeguas JA, Sostres C, Castillo J, Aínsa JA, Díaz-de-Villegas MD, Lanas Á, Touati E, Sancho J

Link to Pubmed [PMID] – 31244111

J. Med. Chem. 2019 Jul;62(13):6102-6115

() infection is the main cause of peptic ulcer and gastric cancer. eradication rates have fallen due to increasing bacterial resistance to currently used broad-spectrum antimicrobials. We have designed, synthesized, and tested redox variants of nitroethylene- and 7-nitrobenzoxadiazole-based inhibitors of the essential protein flavodoxin. Derivatives of the 7-nitrobenzoxadiazole lead, carrying reduced forms of the nitro group and/or oxidized forms of a sulfur atom, display high therapeutic indexes against several reference strains. These inhibitors are effective against metronidazole-, clarithromycin-, and rifampicin-resistant clinical isolates. Their toxicity for mice after oral administration is low, and, when administered individually at single daily doses for 8 days in a mice model of infection, they decrease significantly gastric colonization rates and are able to eradicate the infection in up to 60% of the mice. These flavodoxin inhibitors constitute a novel family of -specific antimicrobials that may help fight the constant increase of antimicrobial-resistant strains.

https://www.ncbi.nlm.nih.gov/pubmed/31244111