In the title compound, C(22)H(16)Cl(2)N(2)O(5), the nearly planar four-membered β-lactam ring [maximum deviations of 0.011 (2) for the N atom] makes dihedral angles of 68.34 (13), 83.04 (13) and 3.37 (13)° with the dichloro-, nitro- and meth-oxy-phenyl rings, respectively. The crystal structure is stabilized by C-H⋯O hydrogen-bond inter-actions. In addition, a π-π stacking inter-action [centroi...

PEPT1 and PEPT2 are H+-coupled peptide transporters expressed preferentially in the intestine and kidney, respectively, which mediate uphill transport of oligopeptides and peptide-like drugs such as β-lactam antibiotics. In the present study, we have compared the recognition of β-lactam antibiotics by LLC-PK1 cells stably transfected with PEPT1 or PEPT2 cDNA. Cyclacillin (aminopenicillin) and c...

Twelve novel β-lactams were synthesized and their antiproliferative effects and binding affinity for the predominant isoforms of the estrogen receptor (ER), ERα and ERβ, were determined. β-Lactams 23 and 26 had the strongest binding affinities for ERα (IC50 values: 40 and 8 nM, respectively) and ERβ (IC50 values: 19 and 15 nM). β-Lactam 26 was the most potent in antiproliferative assays using M...

Community acquired pneumonia (CAP) is increasing in incidence, and is presently responsible for about 1% of emergency medical admissions with an associated mortality of between 5% and 24%. Improving the outcome of CAP is, therefore, a major health priority, but what is the best method to do this? Many audits have shown poor adherence to national guidelines for the management of CAP, with the in...

The β-lactam ring of the title compound, C(26)H(25)ClN(2)O(4), is nearly planar (r.m.s. deviation = 0.025 Å) and the morpholine ring adopts a chair conformation. The mean plane of the β-lactam ring makes dihedral angles of 21.6 (4), 84.4 (4) and 33.7 (4)° with the two benzene rings and the phenyl ring, respectively. The conformation of the title compound is stabilized by intra-molecular C-H⋯O a...

The benefits of β-lactam/macrolide combination therapy over β-lactam therapy alone for the treatment of hospitalised community-acquired pneumonia (CAP) in relation to pneumonia severity are uncertain. We studied 5240 adults hospitalised with CAP from 72 secondary care trusts across England and Wales. The overall 30-day inpatient (IP) death rate was 24.4%. Combination therapy was prescribed in 3...

New Delhi metallo-β-lactamase (NDM-1) is a new metallo-β-lactamase (MBL) that has recently emerged as a global threat because it confers bacteria with resistance to almost all clinically used β-lactam antibiotics. To determine the molecular basis of this threat, NDM-1 was purified from Escherichia coli TransB (DE3) carrying cloned blaNDM-1 gene by an anion-exchange chromatography step followed ...

SYN-004 (ribaxamase) is a β-lactamase designed to be orally administered concurrently with intravenous β-lactam antibiotics, including most penicillins and cephalosporins. Ribaxamase's anticipated mechanism of action is to degrade excess β-lactam antibiotic that is excreted into the small intestine. This enzymatic inactivation of excreted antibiotic is expected to protect the gut microbiome fro...

New Delhi metallo-β-lactmase-1 (NDM-1) has recently attracted extensive attention for its biological activities to catalyze the hydrolysis of almost all of β-lactam antibiotics. To study the catalytic property of NDM-1, the steady-kinetic parameters of NDM-1 toward several kinds of β-lactam antibiotics have been detected. It could effectively hydrolyze most β-lactams (k cat/K m ratios between 0...

Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of fatal bacterial infections in hospitals and has become a global health threat. Although the resistance mechanisms of β-lactam antibiotics have been studied for decades, there are few attempts at systems-wide investigations into how the bacteria respond to antibiotic stress. Spectral counting-based label-free quantitative...