Densely Functionalized 2-Methylideneazetidines: Evaluation as Antibacterials

Twenty-two novel, variously substituted nitroazetidines were designed as both sulfonamide and urethane vinylogs possibly endowed with antimicrobial activity. The compounds under study were obtained following a general procedure recently developed, starting from 4-nitropentadienoates deriving from a common β-nitrothiophenic precursor. While being devoid of any activity against fungi and Gram-negative bacteria, most of the title compounds performed as potent antibacterial agents on Gram-positive bacteria (E. faecalis and three strains of S. aureus), with the most potent congener being the 1-(4-chlorobenzyl)-3-nitro-4-(p-tolyl)azetidine 22, which displayed potency close to that of norfloxacin, the reference antibiotic (minimum inhibitory concentration values 4 and 1–2 μg/mL, respectively). Since 22 combines a relatively efficient activity against Gram-positive bacteria and a cytotoxicity on eucharyotic cells only at 4-times higher concentrations (inhibiting concentration on 50% of the cultured eukaryotic cells: 36 ± 10 μM, MIC: 8.6 μM), it may be considered as a promising hit compound for the development of a new series of antibacterials selectively active on Gram-positive pathogens. The relatively concise synthetic route described herein, based on widely available starting materials, could feed further structure–activity relationship studies, thus allowing for the fine investigation and optimization of the toxico-pharmacological profile.     

Interaction of Moxifloxacin with Bovine Hemoglobin and Effect of the Coexistent Drugs on the Reaction

The interaction between moxifloxacin (MXFX) and Bovine Hemoglobin (BHb) was investigated at different temperatures by fluorescence spectroscopy. Results showed that the quenching mechanism of MXFX on BHb was a static quenching process with Förester spectroscopy energy transfer. The primary binding for MXFX was located at β-37 Tryptophan residue in hydrophobic cavity of BHb. Besides, weak negative cooperativity was found in drug's binding with BHb. Synchronous spectra revealed that the microenvironment and the conformation of serum albumin were changed during the reaction. Most antibiotics had no effect on the system of BHb-MXFX, except quinolone antibiotics. The system had good stability.     

A light scattering and fluorescence emission coupled ratiometry using the interaction of functional CdS quantum dots with aminoglycoside antibiotics as a model system

Any signals, if their intensities have simple functional relationship with analyte concentration, can be applied to analytical purposes. Rayleigh light scattering signals and fluorescence signals are twins in flurospectroscopy, so the light scattering signals are the major interference when the Stokes shift is small. Herein, we propose a light scattering and fluorescence emission (LS-FL) coupled ratiometry using CdS quantum dots (QDs) as a fluorescence probe to detect aminoglycoside antibiotics (AGs). As model analytes, AGs, when attached to the surface of CdS-QDs via electrostatic interaction in aqueous medium, result in strong enhanced light scattering (LS) emission characterized at 376 nm and fluorescence quenching of CdS-QDs at 500 nm. Thus, a ratiometry using the coexistent light scattering and fluorescent emission signals has been proposed. Based on the linear relationship between logarithm of light scattering and fluorescence emission ratio (R) and logarithm of AGs concentration, a novel assay of AGs is established with the limits of detection (3σ) being 58-190 nmol l⁻¹, and applied successfully to detect AGs injection and serum samples.     

Preparation of 14,36-didehydro pristinamycins IIs

The first successful preparation of 14,36-didehydro pristinamycins II_A and II_B is reported via different strategies.     

High performance thin-layer chromatography of some sixteen-membered ring macrolide antibiotics

The use of HPTLC in the analysis of some sixteen-membered ring macrolide antibiotices was examined. In the case of Spiramycins, instrumentalized HPTLC proved to be very efficient for the separation and determination of these antibiotics. With the use of an internal standard together with the datapair technique in sampling and evaluation of the HPTLC plates, a coefficient of variation less than 1.5% could be achieved when determining the different Spiramycins. Other sixteen-membered macrolides, such as Tylosins, Turimycins and 9-Propionylmaridomycins can be separated with sufficient resolution for quantitative work, in spite of their extremely simular structures and large molecular weights. Detection is always at wavelengths which agree with the intrinsic absorption maximum of the chromophors of the components (e. g. 282 nm for Tylosins, 232 nm for Spiramycins and Turimycins, 195 nm for 9-Propionylmaridomycins).     

Biomimetic hydrolysis of penicillin G catalyzed by dinuclear zinc(II) complexes: structure-activity correlations in beta-lactamase model systems

A series of highly preorganized pyrazolate-based dinuclear zinc complexes has been studied as functional synthetic analogues of metallo-beta-lactamases, a class of bacterial enzymes that cause serious clinical problems because of their degradation of common beta-lactam antibiotics. We have investigated the hydrolytic cleavage of penicillin G mediated by the different dinuclear zinc complexes, and have deduced structure-activity correlations. While cooperative effects of the adjacent metal ions might be operative, these are found to either enhance or diminish beta-lactamase activity with respect to a single free zinc. Drastic differences in activity are ascribed to a lack of accessible binding sites after incorporation of the substrate within the bimetallic pocket of 2 and 4, whereas partial detachment of hemilabile ligand side arms in 1 and 3 opens up available coordination sites for nucleophile activation and/or for binding and polarisation of the beta-lactam amide oxygen atom. This interpretation has been corroborated by NMR spectroscopic and mass spectrometric evidence as well as by X-ray crystallography of several adducts formed between the pyrazolate-based dinuclear zinc scaffolds and the small substrate analogue oxazetidinylacetate (oaa), 5-7. In all adducts, the carboxylate group of oaa is the primary anchoring site and is nested in a bridging position within the bimetallic pocket. However, zinc binding of the beta-lactam amide oxygen atom has been confirmed crystallographically for the first time in 7, in which additional open-site coordination sites are available.