-
Inhibitors of O-acetylserine sulfhydrylase with a cyclopropane-carboxylic acid scaffold are effective colistin adjuvants in gram negative bacteria [Elektronski vir]Annunziato, Giannamaria ...Antibacterial adjuvants are of great significance, since they allow one to downscale the therapeutic dose of conventional antibiotics and reduce the insurgence of antibacterial resistance. Herein, we ... report that O-acetylserine sulfhydrylase (OASS) inhibitors could be used as colistin adjuvants to treat infections caused by critical pathogens spreading worldwide, Escherichia coli, Salmonella enterica serovar Typhimurium, and Klebsiella pneumoniae. Starting from a hit compound endowed with a nanomolar dissociation constant, we have rationally designed and synthesized a series of derivatives to be tested against S. Typhimurium OASS isoenzymes, StOASS-A and StOASS-B. All acidic derivatives have shown good activities in the nanomolar range against both OASS isoforms in vitro. Minimal Inhibitory Concentrations (MICs) were then evaluated, as well as compounds’ toxicity. The compounds endowed with good activity in vitro and low cytotoxicity have been challenged as a potential colistin adjuvant against pathogenic bacteria in vitro and the fractional inhibitory concentration (FIC) index has been calculated to define additive or synergistic effects. Finally, the target engagement inside the S. Typhimurium cells was confirmed by using a mutant strain in which the OASS enzymes were inactivated. Our results provide a robust proof of principle supporting OASS as a potential nonessential antibacterial target to develop a new class of adjuvants.Vir: Pharmaceuticals [Elektronski vir]. - ISSN 1424-8247 (Vol. 15, iss. 6, art. 766, 2022, str. 1-24)Vrsta gradiva - e-članek ; neleposlovje za odrasleLeto - 2022Jezik - angleškiCOBISS.SI-ID - 112985091
Avtor
Annunziato, Giannamaria |
Spadini, Costanza |
Marchetti, Marialaura |
Franko, Nina |
Pavone, Marialaura |
Iannarelli, Mattia |
Bruno, Agostino |
Pieroni, Marco, farmacevt |
Bettati, Stefano |
Cabassi, Clotilde Silvia |
Campanini, Barbara |
Costantino, Gabriele
Teme
Protimikrobna zdravila |
Bakterijska rezistenca |
protimikrobna odpornost (AMR) |
odkritje drog |
zaviralci OASS |
protimikrobni adjuvansi |
kolistin |
antimicrobial resistance (AMR) |
drug discovery |
OASS inhibitors |
antimicrobial adjuvants |
colistin
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|---|
Annunziato, Giannamaria | |
Spadini, Costanza | |
Marchetti, Marialaura | |
Franko, Nina | 55258 |
Pavone, Marialaura | |
Iannarelli, Mattia | |
Bruno, Agostino | |
Pieroni, Marco, farmacevt | |
Bettati, Stefano | |
Cabassi, Clotilde Silvia | |
Campanini, Barbara | |
Costantino, Gabriele |
Izberite prevzemno mesto:
Prevzem gradiva po pošti
Obvestilo
Gesla v Splošnem geslovniku COBISS
Izbira mesta prevzema
Mesto prevzema | Status gradiva | Rezervacija |
---|
Prosimo, počakajte trenutek.