title: From triclosan toward the clinic: discovery of nonbiocidal, potent FabI inhibitors for the treatment of resistant bacteria.
abstract: In this paper, we present some elements of our optimization program to decouple triclosan's specific FabI effect from its nonspecific cytotoxic component. The implementation of this strategy delivered highly specific, potent, and nonbiocidal new FabI inhibitors. We also disclose some preclinical data of one of their representatives, 83, a novel antibacterial compound active against resistant staphylococci and some clinically relevant Gram negative bacteria that is currently undergoing clinical trials.
authors.affiliation: Medicinal Chemistry and ‡Biology, Mutabilis, 102 Avenue Gaston Roussel, 93230 Romainville, France. gerusz@mutabilis.fr
authors.forename: Vincent
authors.initials: V
authors.lastname: Gerusz
authors.forename: Alexis
authors.initials: A
authors.lastname: Denis
authors.forename: Fabien
authors.initials: F
authors.lastname: Faivre
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bonvin
authors.forename: Mayalen
authors.initials: M
authors.lastname: Oxoby
authors.forename: Sophia
authors.initials: S
authors.lastname: Briet
authors.forename: Géraldine
authors.initials: G
authors.lastname: LeFralliec
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Oliveira
authors.forename: Nicolas
authors.initials: N
authors.lastname: Desroy
authors.forename: Cédric
authors.initials: C
authors.lastname: Raymond
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Peltier
authors.forename: François
authors.initials: F
authors.lastname: Moreau
authors.forename: Sonia
authors.initials: S
authors.lastname: Escaich
authors.forename: Vanida
authors.initials: V
authors.lastname: Vongsouthi
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Floquet
authors.forename: Elodie
authors.initials: E
authors.lastname: Drocourt
authors.forename: Armelle
authors.initials: A
authors.lastname: Walton
authors.forename: Laure
authors.initials: L
authors.lastname: Prouvensier
authors.forename: Marc
authors.initials: M
authors.lastname: Saccomani
authors.forename: Lionel
authors.initials: L
authors.lastname: Durant
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Genevard
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sam-Sambo
authors.forename: Coralie
authors.initials: C
authors.lastname: Soulama-Mouze
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000138:chemical synthesis / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis / Q000494:pharmacology*; D002478:Cells, Cultured; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014260:Triclosan / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: C577948:4-(4-ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzamide; D000891:Anti-Infective Agents, Local; D001549:Benzamides; D010647:Phenyl Ethers; D014260:Triclosan; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)