Syntheses, and Characterization of Complexes Containing Beta-lactam Group with some Transitional Elements and Study their Biological Activity

In this study, a novel azo-azomethine ligand [6[2-hydroxy-4-((3-nitrophenyl)diazenyl)-1-phenyl]imine penicillanic acid] [HNDIP] is synthesized from [2-hydroxy-4-((3-nitrophenyl)diazenyl) benzaldehyde]. And reflux with 6-aminopenicillin acid, this ligand was identified by UV-Vis, FTIR, 1H-NMR, C13NMR, and mass, and it was used to prepare new complexes with [Cu(II), Ni(II), Co(II), Zn(II), and Fe(II)] metal ions. These complexes were identified by FTIR, UV-Vis, molar conduct, magnetic sensitivity, and atomic absorption for all complexes, the reaction ingredients were observed to be ratio 1:2 (metal: ligand). The ligand, a tridentate with a single negative charge, was coupled with metal ions to form claw complexes, resulting in an octahedral shape. Finally, antibacterial effectiveness was determined for the ligand and complexes against two distinct bacteria strains (Pseudomonas and klebsiella). It was discovered that the ligand and its complexes have high inhibitory activity against bacteria (Pseudomonas and Klebsiella). As a result, the chemicals created may be feasible substitutes for routinely used drugs.

Synthesis, Characterization and Antibacterial Activity of Some Penicillin Derivatives

This study illustrated the synthesis of two new di amidine compounds ([c] and [d]) by reaction of 6-amino penicillanic acid (6-APA) with diα-amino nitrile compounds ([a] and [b]). [a] and [b] di α-amino nitrile compounds synthesized from the condensation reaction on aldehyd and di amine in the presence of potassium cyanid as one pot-three components reaction. The new di amidine compounds ([c] and [d]) have been proven their efficiency by inhibiting some types of bacteria (Staphylococcus aurous, Streptococcus, Escherichia coliand klebsiella). Amidine compound [d] showed better effect than [c] against the selected bacteria.The synthesized compounds were characterized by conventional techniques using infrared spectrophotometer (IR) andproton-nuclear magnetic resonance (1H-NMR)

Synthesis of Antibiotic Penicillin-G Enzymatically by Penicillium chrysogenum

Penicillin-G antibiotic was used as the basic ingredient of making antibiotic type β-lactam such as tetracycline, amoxicillin, ampicillin and other antibiotics. Penicillin-G was splited into 6-amino penicillanic acid as the source of β-lactam. The biosynthetic pathway for the formation of penicillin-G in Penicillium chrysogenum cell through the formation of intermediates was carried out in the form of amino acids such as α-aminoadipate, L-cysteine, L-valine which are formed from glucose (food ingredients).The formation of 6-amino penicillanic acid is an amino acid combination of L-cysteine and L-valine, a step part of the formation of antibiotic penicillin-G in P. chrysogenum cells, thus, it is obvious that there are enzymes involved in its formation. The objective of this study was to examine the use of enzymes present in P. chrysogenum cells to produce penicillin-G and 6-amino penicillanic acid using the intermediate compounds α-aminoadipate, L-cysteine, L-valine and phenylacetic acid assisted by NAFA® coenzymes in P. chrysogenum cells which is more permeable. The research method started from producing biomass of P. chrysogenum cells that demonstrated penicillin-producing antibiotic capability, as the source of the enzyme, followed by addition of permeability treatment of P. chrysogenum cell membrane to get immobile of enzyme by its own cell therefore it can be used more than once. After that the enzyme activity was proven by adding α-aminoadipate, L-cysteine, L-valine, phenylacetic acid and NAFA® coenzyme for the formation of penicillin-G, whereas the addition of L-cystein, L-valine and NAFA® coenzyme were aimed to form 6-amino penicillanic acid. The results showed that P. chrysogenum is able to produce antibiotics with stationary early phase on day 6. The best increased permeability of P. chrysogenum cell membranes was obtained using a 1:4 of toluene:ethanol ratio mixture with the highest antibiotic concentration (130.06 mg/L) after testing for the enzymatic formation of antibacterial penicillin-G.

In Vitro Activity of Cefepime-Enmetazobactam against Gram-Negative Isolates Collected from U.S. and European Hospitals during 2014–2015

ABSTRACT Enmetazobactam, formerly AAI101, is a novel penicillanic acid sulfone extended-spectrum β-lactamase (ESBL) inhibitor. The combination of enmetazobactam with cefepime has entered clinical trials to assess safety and efficacy in patients with complicated urinary tract infections. Here, the in vitro activity of cefepime-enmetazobactam was determined for 1,993 clinical isolates of Enterobacteriaceae and Pseudomonas aeruginosa collected in the United States and Europe during 2014 and 2015. Enmetazobactam at a fixed concentration of 8 μg/ml lowered the cefepime MIC90 from 16 to 0.12 μg/ml for Escherichia coli, from >64 to 0.5 μg/ml for Klebsiella pneumoniae, from 16 to 1 μg/ml for Enterobacter cloacae, and from 0.5 to 0.25 μg/ml for Enterobacter aerogenes. Enmetazobactam did not enhance the potency of cefepime against P. aeruginosa. Applying the Clinical and Laboratory Standards Institute susceptible-dose-dependent (SDD) breakpoint of 8 μg/ml to cefepime-enmetazobactam for comparative purposes resulted in cumulative inhibitions of 99.9% for E. coli, 96.4% for K. pneumoniae, 97.0% for E. cloacae, 100% for E. aerogenes, 98.1% for all Enterobacteriaceae assessed, and 82.8% for P. aeruginosa. Comparator susceptibilities for all Enterobacteriaceae were 99.7% for ceftazidime-avibactam, 96.2% for meropenem, 90.7% for ceftolozane-tazobactam, 87% for cefepime (SDD breakpoint), 85.7% for piperacillin-tazobactam, and 81.2% for ceftazidime. For the subset of ESBL-producing K. pneumoniae isolates, the addition of 8 μg/ml enmetazobactam to cefepime lowered the MIC90 from >64 to 1 μg/ml, whereas the shift for 8 μg/ml tazobactam was from >64 to 8 μg/ml. Cefepime-enmetazobactam may represent a novel carbapenem-sparing option for empirical treatment of serious Gram-negative infections in settings where ESBL-producing Enterobacteriaceae are expected.

Beyond Piperacillin-Tazobactam: Cefepime and AAI101 as a Potent β-Lactam−β-Lactamase Inhibitor Combination

ABSTRACTImpeding, as well as reducing, the burden of antimicrobial resistance in Gram-negative pathogens is an urgent public health endeavor. Our current antibiotic armamentarium is dwindling, while major resistance determinants (e.g., extended-spectrum β-lactamases [ESBLs]) continue to evolve and disseminate around the world. One approach to attack this problem is to develop novel therapies that will protect our current agents. AAI101 is a novel penicillanic acid sulfone β-lactamase inhibitor similar in structure to tazobactam, with one important difference. AAI101 possesses a strategically placed methyl group that gives the inhibitor a net neutral charge, enhancing bacterial cell penetration. AAI101 paired with cefepime, also a zwitterion, is in phase III of clinical development for the treatment of serious Gram-negative infections. Here, AAI101 was found to restore the activity of cefepime against class A ESBLs (e.g., CTX-M-15) and demonstrated increased potency compared to that of piperacillin-tazobactam when tested against an established isogenic panel. The enzymological properties of AAI101 further revealed that AAI101 possessed a unique mechanism of β-lactamase inhibition compared to that of tazobactam. Additionally, upon reaction with AAI101, CTX-M-15 was modified to an inactive state. Notably, thein vivoefficacy of cefepime-AAI101 was demonstrated using a mouse septicemia model, indicating the ability of AAI101 to bolster significantly the therapeutic efficacy of cefepimein vivo. The combination of AAI101 with cefepime represents a potential carbapenem-sparing treatment regimen for infections suspected to be caused byEnterobacteriaceaeexpressing ESBLs.