ABSTRACT
In an effort to develop new fluoroquinolones, we synthesized eight compounds and tested them against a panel of bacteria. The design of these compounds was guided by the introduction of the isothiazoloquinolone motif. The three most active compounds in this series, 8-10, demonstrated good antibacterial activity against methicillin-sensitive Staphylococcus aureus and healthcare-acquired methicillin-resistant Staphylococcus aureus (MIC 0.62-6.3 µg/mL). Further, when these three active compounds were tested for their inhibitory effects on bacterial enzymes, compound 9 was the most effective agent exhibiting IC50 values of 33.9 and 116.5 µM in the S. aureus deoxyribonucleic acid (DNA) gyrase supercoiling and topoisomerase IV decatenation assays, respectively.
Subject(s)
Amides/pharmacology , Anti-Bacterial Agents/pharmacology , Fluoroquinolones/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Thiazoles/pharmacology , Thiazolidines/pharmacology , Amides/chemical synthesis , Amides/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Dose-Response Relationship, Drug , Fluoroquinolones/chemical synthesis , Fluoroquinolones/chemistry , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship , Thiazoles/chemical synthesis , Thiazoles/chemistry , Thiazolidines/chemical synthesis , Thiazolidines/chemistryABSTRACT
BACKGROUND AND STUDY AIMS: Capsule endoscopy is an attractive alternative to colorectal cancer screening by conventional colonoscopy, but is currently limited by compromised mucosal visibility because of the lack of safe, controlled colonic insufflation. We have therefore developed a novel system of untethered, wireless-controlled carbon dioxide (CO2) insufflation for use in colonic capsule endoscopy, which this study aims to assess in vivo. MATERIAL AND METHODS: This observational, nonsurvival, in vivo study used five Yorkshire-Landrace cross swine. A novel insufflation capsule was placed in the porcine colons, and we recorded volume of insufflation, time, force, visualization, and a pathologic assessment of the colon. RESULTS: The mean (standard deviation [SD]) diameter of insufflation was 32.1 (3.9)âmm. The volume of CO2 produced successfully allowed complete endoscopic visualization of the mucosa and safe proximal passage of the endoscope. Pathologic examination demonstrated no evidence of trauma caused by the capsule. CONCLUSIONS: These results demonstrate the feasibility of a novel method of controlled colonic insufflation via an untethered capsule in vivo. This technological innovation addresses a critical need in colon capsule endoscopy.
Subject(s)
Capsule Endoscopy/methods , Colon/pathology , Colonoscopy/methods , Insufflation/methods , Intestinal Mucosa/pathology , Animals , Capsule Endoscopy/instrumentation , Carbon Dioxide/administration & dosage , Colonoscopy/instrumentation , Feasibility Studies , Female , Insufflation/instrumentation , SwineABSTRACT
Transformations of functional groups, such as OCH2Ph, OCOPh, NO2 and I, in 1,3,5-triphenyl-6-oxoverdazyls 1a-1e were investigated in order to expand the range of synthetic tools for incorporation of the verdazyl system into more complex molecular architectures and to increase spin delocalization. Thus, Pd-catalyzed debenzylation of the OCH2Ph group or basic hydrolysis of the OCOPh group gave the phenol functionality, which was acylated, but could not be alkylated. Orthogonal deprotection of diphenol functionality was also demonstrated in radical 1c. Pt-catalyzed reduction of the NO2 group led to the aniline derivative, which was acylated. Attempted C-C coupling reactions to iodophenyl derivatives 1e and 5e were unsuccessful. Selected verdazyl radicals were characterized by EPR and electronic absorption spectroscopy, and results were analyzed with the aid of DFT computational methods.
