Antiadhesion Therapy for Urinary Tract Infections-A Balanced PK/PD Profile Proved To Be Key for Success was written by Jiang, Xiaohua;Abgottspon, Daniela;Kleeb, Simon;Rabbani, Said;Scharenberg, Meike;Wittwer, Matthias;Haug, Martina;Schwardt, Oliver;Ernst, Beat. And the article was included in Journal of Medicinal Chemistry in 2012.Reference of 754214-56-7 This article mentions the following:
The initial step for the successful establishment of urinary tract infections (UTIs), predominantly caused by uropathogenic Escherichia coli, is the adhesion of bacteria to urothelial cells. This attachment is mediated by FimH, a mannose-binding adhesin, which is expressed on the bacterial surface. To date, UTIs are mainly treated with antibiotics, leading to the ubiquitous problem of increasing resistance against most of the currently available antimicrobials. Therefore, new treatment strategies are urgently needed, avoiding selection pressure and thereby implying a reduced risk of resistance. Here, we present a new class of highly active antimicrobials, targeting the virulence factor FimH. When the most potent representative, an indolinylphenyl mannoside, was administered in a mouse model at the low dosage of 1 mg/kg (corresponding to approx. 25 μg/mouse), the minimal therapeutic concentration to prevent UTI was maintained for more than 8 h. In a treatment study, the colony-forming units in the bladder could be reduced by almost 4 orders of magnitude, comparable to the standard antibiotic treatment with ciprofloxacin (8 mg/kg, s.c.). In the experiment, the researchers used many compounds, for example, 7-Azaindole-5-boronic Acid Pinacol Ester (cas: 754214-56-7Reference of 754214-56-7).
7-Azaindole-5-boronic Acid Pinacol Ester (cas: 754214-56-7) belongs to indole derivatives. Indole, first isolated in 1866, and it is commonly synthesized from phenylhydrazine and pyruvic acid, although several other procedures have been discovered. Indole plays a fundamental role for QS in E. coli, being one of the signal molecules responsible for the transcription of a variety of genes (gabT, and tnaB ASTD). Reference of 754214-56-7
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles