Mannose‐Binding Geometry of Pradimicin A

Pradimicins (PRMs) and benanomicins are the only family of non‐peptidic natural products with lectin‐like properties, that is, they recognize D ‐mannopyranoside (Man) in the presence of Ca²⁺ ions. Coupled with their unique Man binding ability, they exhibit antifungal and anti‐HIV activities through binding to Man‐containing glycans of pathogens. Notwithstanding the great potential of PRMs as the lectin mimics and therapeutic leads, their molecular basis of Man recognition has yet to be established. Their aggregate‐forming propensity has impeded conventional interaction analysis in solution, and the analytical difficulty is exacerbated by the existence of two Man binding sites in PRMs. In this work, we investigated the geometry of the primary Man binding of PRM‐A, an original member of PRMs, by the recently developed analytical strategy using the solid aggregate composed of the 1:1 complex of PRM‐A and Man. Evaluation of intermolecular distances by solid‐state NMR spectroscopy revealed that the C2–C4 region of Man is in close contact with the primary binding site of PRM‐A, while the C1 and C6 positions of Man are relatively distant. The binding geometry was further validated by co‐precipitation experiments using deoxy‐Man derivatives, leading to the proposal that PRM‐A binds not only to terminal Man residues at the non‐reducing end of glycans, but also to internal 6‐substituted Man residues. The present study provides new insights into the molecular basis of Man recognition and glycan specificity of PRM‐A.     

Amoxicillin removal from aqueous matrices by sorption with almond shell ashes

The adsorption of the antibiotic amoxicillin at low concentration levels (µg?L^?1 order) from aqueous solution on almond shell ashes has been investigated, either by kinetic or equilibrium assays. The effect of the adsorbent amount, initial concentration of the antibiotic, particle diameter (d_p) and temperature were considered to evaluate the adsorption capacity of the adsorbent. The results showed that amoxicillin sorption is dependent on these four factors. The adsorption process was relatively fast and equilibrium was established in about 12 hours. The optimum parameters for an initial concentration of 450?µg?L^?1 were 50?mg of adsorbent, 303?K and d_p?<?600?µm. A comparison of kinetic models showed that pseudo-second order kinetics provides the best correlation of the experimental data. Isotherm data adjusted better to Langmuir equation, with an adsorption capacity of 2.5?±?0.1?mg?g^?1 at 303?K. The desorption process was also evaluated (maximum efficiency of 5%). Thermodynamic parameters were calculated and the negative value of ΔH⁰ and ΔG⁰ showed that adsorption was exothermic and a spontaneous process.     

Development and validation of a rapid assay based on liquid chromatography–tandem mass spectromtetry for determining macrolide antibiotic residues in eggs

A simple and rapid method able to determine residues of erythromycin A, tylosin and tilmicosin in whole eggs is presented here. The analytical protocol involves a one-step extraction followed by liquid chromatography (LC)–tandem mass spectrometry. Analytes were extracted from 1 g of egg spiked with an internal standard (josamycin) with acetonitrile. In terms of accuracy, matrix effect and ion signal stability, no extract cleanup was found to be necessary. After partial solvent removal, the final extract was injected into the LC column. Extraction was effective, since absolute recovery of the analyte in egg at their maximum residue limit (MRL) level was 85–102%. Estimated limits of quantification (S/N = 10) were 0.2–0.5 ng/g. Based on the EU Commission Decision 2002/657/EC, the method was in-house validated in terms of ruggedness, specificity, linearity, within-laboratory reproducibility, decision limit (CCα) and detection capability (CCβ). The within-laboratory reproducibility, expressed as RSD (n = 18 at the MRL levels), was not higher than 13%. After validation, a short study on EA depletion in eggs was conducted after administration of this drug to laying hens.     

大环抗生素--毛细管电泳手性分离中一种新的手性选择剂

两种类型的大环抗生素对很多外消旋化合物具有显著的手性选择性且手性选择性相互补充:第一种类型含ansamycin (安沙霉素) 特别适合于阳离子外消旋化合物的分离;第二种类型含glycopeptide (糖肽)最适于阴离子的分离.介绍了大环抗生素的结构特征及手性识别机理,讨论了pH值、抗生素类型和浓度、电泳电解质浓度和化学性质、有机改性剂及胶束相等不同实验条件对分离的影响,还概述了几种大环抗生素作为手性选择剂,在毛细管电泳手性分离中的研究近况.     

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.     

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.