A series of novel 6-fluoro1,4-dihydro-4-oxo-3-quinoline carboxylic acid dimers were synthesized as potential antibacterial agents from commercially available substituted fluorobenzoic acids. A stability indicating HPLC method was developed to determine these novel fluoroquinolone dimers using a systematic method development approach. Samples were subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation; and analyzed to demonstrate the specificity and stability indicating ability of the developed method. The precision for all four fluoroquinolone dimers was within 2.0% RSD. Calibration curves were linear (LOQ, 150%), with regression coefficients >0.99 for all dimers. The method was conveniently applied for determining purity and assay of these four novel fluoroquinolone dimers.
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http://dx.doi.org/10.1016/j.jpba.2011.09.025 | DOI Listing |
Infect Drug Resist
December 2024
Department of Infectious Diseases, Shaoxing People's Hospital, Shaoxing, Zhejiang, People's Republic of China.
Purpose: Psittacosis is an often-neglected cause of community acquired pneumonia (CAP). The limited diagnostic methods for psittacosis pneumonia invariably result in an unfavourable prognosis. Consequently, the early detection of psittacosis pneumonia is crucial.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Department of Molecular Microbiology, John Innes Centre, Norwich NR4 7UH, United Kingdom.
Type II topoisomerase DNA gyrase transduces the energy of ATP hydrolysis into the negative supercoiling of DNA. The postulated catalytic mechanism involves stabilization of a chiral DNA loop followed by the passage of the T-segment through the temporarily cleaved G-segment resulting in sign inversion. The molecular basis for this is poorly understood as the chiral loop has never been directly observed.
View Article and Find Full Text PDFThere remains a clinical need for better approaches to rapid drug susceptibility testing in view of the increasing burden of multidrug resistant tuberculosis. Binary susceptibility phenotypes only capture changes in minimum inhibitory concentration when these cross the critical concentration, even though other changes may be clinically relevant. We developed a machine learning system to predict minimum inhibitory concentration from unassembled whole-genome sequencing data for 13 anti-tuberculosis drugs.
View Article and Find Full Text PDFElife
June 2024
Department Biochemistry & Metabolism, John Innes Centre, Norwich Research Park, Norwich, United Kingdom.
ACS Med Chem Lett
July 2023
China Innovation Center of Roche, Roche R&D Center (China) Ltd., Shanghai 201203, China.
The rise of multidrug-resistant (MDR) Gram-negative bacteria is a major global health problem necessitating the discovery of new classes of antibiotics. Novel bacterial topoisomerase inhibitors (NBTIs) target the clinically validated bacterial type II topoisomerases with a distinct binding site and mechanism of action to fluoroquinolone antibiotics, thus avoiding cross-resistance to this drug class. Here we report the discovery of a series of NBTIs incorporating a novel indane DNA binding moiety.
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