Search results for "Beta-Lactamase Inhibitors"
showing 6 items of 6 documents
Preparation of Carbon-14 Labeled 2-(2-mercaptoacetamido)-3-phenylpropanoic Acid as Metallo-beta-lactamases Inhibitor (MBLI), for Coadministration wit…
2019
Aim and Objective: Bacteria could become resistant to β-lactam antibiotics through production of β- lactamase enzymes like metallo-β-lactamase. 2-(2-mercaptoacetamido)-3-phenylpropanoic acid was reported as a model inhibitor for this enzyme. In order to elucidate the mechanism of action in the body’s internal environment, preparation of a labeled version of 2-(2-mercaptoacetamido)-3-phenylpropanoic acid finds importance. In this regard, we report a convenient synthetic pathway for preparation of carbon-14 labeled 2-(2- mercaptoacetamido)-3-phenylpropanoic acid. Materials and Methods: This study was initiated by using non-radioactive materials. Then, necessary characterization was performed…
Case-specific performance of MM-PBSA, MM-GBSA, and SIE in virtual screening.
2015
In drug discovery the reliable prediction of binding free energies is of crucial importance. Methods that combine molecular mechanics force fields with continuum solvent models have become popular because of their high accuracy and relatively good computational efficiency. In this research we studied the performance of molecular mechanics generalized Born surface area (MM-GBSA), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), and solvated interaction energy (SIE) both in their virtual screening efficiency and their ability to predict experimentally determined binding affinities for five different protein targets. The protein-ligand complexes were derived with two different app…
Pharmaceutical Approaches to Target Antibiotic Resistance Mechanisms
2017
There is urgent need for new therapeutic strategies to fight the global threat of antibiotic resistance. The focus of this Perspective is on chemical agents that target the most common mechanisms of antibiotic resistance such as enzymatic inactivation of antibiotics, changes in cell permeability, and induction/activation of efflux pumps. Here we assess the current landscape and challenges in the treatment of antibiotic resistance mechanisms at both bacterial cell and community levels. We also discuss the potential clinical application of chemical inhibitors of antibiotic resistance mechanisms as add-on treatments for serious drug-resistant infections. Enzymatic inhibitors, such as the deriv…
Comparative trial between the use of amoxicillin and amoxicillin clavulanate in the removal of third molars
2014
Objectives: The purpose of this study was to compare the use of amoxicillin (1g) vs amoxicillin and clavulanate (875/125mg) after extraction of retained third molars for prevention of infectious complications. Study Design: The study involved 546 patients attending for removal a retained third molar and divided in to two groups: Group 1 - amoxicillin and clavunate (875/125mg) group (n=257) and Group 2 - amoxicillin (1g) group (n=289). All patients were recalled for investigating the possibility of infection, presence of diarrhea and further analgesic intake. Results: From a total of 546 patients, the frequency of infection was 1.4%, without no statistically differences be - tween the two gr…
New β-Lactam-β-Lactamase Inhibitor Combinations.
2020
The limited armamentarium against drug-resistant Gram-negative bacilli has led to the development of several novel β-lactam-β-lactamase inhibitor combinations (BLBLIs). In this review, we summarize their spectrum of in vitro activities, mechanisms of resistance, and pharmacokinetic-pharmacodynamic (PK-PD) characteristics. A summary of available clinical data is provided per drug. Four approved BLBLIs are discussed in detail. All are options for treating multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa Ceftazidime-avibactam is a potential drug for treating Enterobacterales producing extended-spectrum β-lactamase (ESBL), Klebsiella pneumoniae carbapenemase (KPC), AmpC, an…
In silico identification and experimental validation of hits active against KPC-2 β-lactamase
2018
Bacterial resistance has become a worldwide concern, particularly after the emergence of resistant strains overproducing carbapenemases. Among these, the KPC-2 carbapenemase represents a significant clinical challenge, being characterized by a broad substrate spectrum that includes aminothiazoleoxime and cephalosporins such as cefotaxime. Moreover, strains harboring KPC-type β-lactamases are often reported as resistant to available β-lactamase inhibitors (clavulanic acid, tazobactam and sulbactam). Therefore, the identification of novel non β-lactam KPC-2 inhibitors is strongly necessary to maintain treatment options. This study explored novel, non-covalent inhibitors active against KPC-2, …