Novel C-7 carbon substituted fourth generation fluoroquinolones targeting N. Gonorrhoeae infections.

Delafloxacin, a fourth-generation anionic fluoroquinolone (FQ) was approved in 2019 for community acquired bacterial pneumonia (CARP). It has broad spectrum activity and an improved class-related toxicity profile. However, it has recently failed a Phase 3 clinical trial for treatment of N.

Efficacy of a Novel Tricyclic Topoisomerase Inhibitor in a Murine Model of Neisseria gonorrhoeae Infection.

There is an urgent need for new antibiotics to treat multidrug-resistant Neisseria gonorrhoeae In this report, the microbiology, in vivo pharmacokinetics, and efficacy of REDX05931, a representative novel tricyclic topoisomerase inhibitor, were evaluated. REDX05931 demonstrated high oral bioavailability in mice and reduced N. gonorrhoeae infection after a single dose in a mouse model of gonorrhea.

Biological profiling of novel tricyclic inhibitors of bacterial DNA gyrase and topoisomerase IV.

Objectives: The objective of this study was to characterize the in vitro and in vivo biological properties of a novel series of small-molecule bacterial type IIA topoisomerase inhibitors.

Methods: Bacterial susceptibility testing was performed by broth microdilution. Resistance frequencies were determined by plating bacteria onto agar containing test compound and enumerating mutants.

Trifluoroibuprofen inhibits α-methylacyl coenzyme A racemase (AMACR/P504S), reduces cancer cell proliferation and inhibits in vivo tumor growth in aggressive prostate cancer models.

Background: α-Methylacyl-CoA racemase (AMACR) participates in the oxidation of branched chain fatty acids and is highly expressed in prostate cancer (PCa). The aims of this study were to verify if the AMACR inhibitor trifluoroibuprofen (TFIP) had anticancer effects and to determine the best route for in vivo administration.

Materials And Methods: In vitro effects of TFIP were verified by using three non-tumour prostate epithelial cell lines, a series of eight PCa cell lines and six cell derivatives.

Inhibition of human α-methylacyl CoA racemase (AMACR): a target for prostate cancer.

The enzyme α-methylacyl CoA racemase (AMACR) is involved in the metabolism of branched-chain fatty acids and has been identified as a promising therapeutic target for prostate cancer. By using the recently available human AMACR from HEK293 kidney cell cultures, we tested a series of new rationally designed inhibitors to determine the structural requirements in the acyl component. An N-methylthiocarbamate (Ki=98 nM), designed to mimic the proposed enzyme-bound enolate, was found to be the most potent AMACR inhibitor reported to date.