Series Of Β-lactams Research Articles

Visualized characterization of bacterial penicillin G acylase for the hydrolysis of β-lactams using an activatable NIR fluorescent probe

Penicillin G acylase (PGA) identified from bacteria, is used as industrial biocatalyst for the hydrolysis of penicillins along with the production of 6-aminopenicillanic acid, a key intermediate of the semi-synthetic β-lactam antibiotics. Due to wide usage of PGA, some novel homology bioactive enzymes are investigated in various bacteria, and visualized analysis technique would be necessary and helpful for the development and utilization of PGA function in living systems. In the present work, an activated off-on near-infrared (NIR) fluorescent probe (DDAP) deduced from a novel fluorophore has been designed and developed for sensitively and selectively detecting endogenous PGA in real-time. The hydrolysis mechanism has been elucidated using in silico docking analysis, which confirmed DDAP as the specific substrate of PGA. Using DDAP as the fluorescent probe, the endogenous bacterial PGA was imaged in living systems successfully, which could be applied to identify bacteria with PGA expression from complex microorganism samples. Furthermore, using DDAP as the staining agent, the endogenous PGA in various bacteria has been profiled visually on native-PAGE gel, and the PGA activity in bacterial lysates could be effectively determined. The PAGE-gel for PGA analysis stained by DDAP was more sensitive than generally used silver and Coomassie Blue dyes. Finally, a series of β-lactams were hydrolyzed by recombinant PGA to further confirm its hydrolase property, corresponding to the hydrolysis of DDAP.

A New Approach Using Aromatic-Solvent-Induced Shifts in NMR Spectroscopy to Analyze β-Lactams with Various Substitution Patterns

The chemical shifts of protons depend not only on the properties of the solute molecule but also on the medium in which the solute resides. A series of β-lactams with various substitution patterns were synthesized to study aromatic-solvent-induced shifts (ASISs) in chloroform and benzene by using 1H NMR spectroscopy. The results agreed with those obtained by theoretical density functional theory calculations. The protons of the β-lactam ring are the most affected by the ASIS effect, and they tend to overlap due to the anisotropic effect of benzene.

One-pot synthesis of trans-β-lactams from ferrocenylketene generated by thermal Wolff rearrangement

ABSTRACTA series of β-lactams containing the ferrocene moiety were synthesized through the Staudinger reaction between ferrocenylketene generated by the thermal Wolff rearrangement of the corresponding diazo ketone and various imines. The stereochemical outcome has been investigated and the trans-products were isolated as the main products, opposite to the reported results by Bonini and coworkers. The absolute configuration of (±)-trans-1,4-diphenyl-3-ferrocenylazetidin-2-one (3c) was determined by X-ray analysis. The stereoselectivity is discussed from the viewpoint of the reaction mechanism.

Evaluation of newly isolated human vaginal lactobacilli and selection of probiotic candidates

The probiotic relevant characteristics of 45 strains of vaginal Lactobacillus isolated from healthy women were analyzed. 21 of them were classified as L. crispatus , 17 as L. jensenii , 6 as L. gasseri and one as L. plantarum . The rate of acidification varied significantly between the strains as did the ability to form biofilms. None used glycogen as a fermentable carbohydrate. Generation of H2O2 was common, being especially frequent among L. jensenii isolates (88%). No bacteriocinogenic strains were detected. Most strains harboured plasmids (between 1 and 7) of various sizes, those in excess of 50 kb being frequent. One of these plasmids was found to be promiscuous since it hybridized with extrachromosomal bands of 15 isolates. All strains were resistant to metronidazole, ciprofloxacin, gentamicin, clindamycin, trimethoprim and sulfametoxazole and susceptible to a series of β-lactams, erythromycin, tetracycline and benzalkonium chloride. Furthermore, no amplification was found with primers that matched a series of tetracycline and erythromycin resistance genes. Almost half of the strains were highly resistant to nonoxinol 9, which is commonly used as a spermicide. Based on these analysis strains of all three common species are proposed as new probiotic candidates.

AM1 heats of formation for the reaction of alcohols with a series of β-lactams and aza-β-lactams: Design of novel β-lactamase inactivators

AM1 heats of formation (H f) for the reaction of MeOH and EtOH with a series of β-lactams and aza-β-lactams are calculated. The ΔH f values for hemi-acetal and acyl/carbamoyl-enzyme intermediate formation are compared in the two series. These model calculations predict that the reaction of the β-lactamase active site serine hydroxyl with aza-β-lactams will afford carbamate intermediates which should be refractory to hydrolysis, thereby inhibiting the enzyme. Therefore, novel aza-β-lactams are putative β-lactamase inactivators based on semi-empirical computations.

Synthesis and biological activity of 4-(N-arylidene acetylhydrazido)-1,4-benzothiazin-2,3-diones, azetidinones and thiazolidinones

1,4-Benzothiazin-2,3-dione (I) on N-methyl ethoxylation with ethyl chloracetate gives (II) which on reaction with hydrazine hydrate yields 4-(acetylhydrazido)-1,4-benzothiazin-2,3-dione (III). This was further condensed with different aldehydes to form the 4-(N-arylidene acetylhydrazido)-1,4-benzothiazin-2,3-dione (IV). These compounds are converted into a series of β-lactams (V) and 4-thiazolidinones (IV). The antibacterial and antifungal activities of the compounds have been determined.