67899-00-7Relevant articles and documents
Discovery of novel β-lactam amalgamated 4-methylthiazole-5-carboxylic acid derivatives as potential antimicrobial agents
Arshad, Mohammed Faiz,Al-Otaibi, Faisal,Kumar, Suresh,Nagarethinam, Sivagurunathan,Elkerdasy, Ahmed,Upmanyu, Neeraj
, p. 1699 - 1709 (2017/12/15)
Penicillin binding proteins are the essential component for the bacterial cell wall synthesis, which has been identified as potential targets for the development of new β-lactam containing antimicrobial agents. In view of this, a series of substituted 2-(2-chloro-3-oxo-4-phenylazetidin-1-yl)-4-methylthiazole-5-carboxylic acid derivatives (5a-r) were synthesized and characterized by FTIR, 1H-NMR, 13C-NMR and mass spectrometry. The synthesized β-lactam ring containing thiazole carboxylic acid derivatives (5a-r) were screened for antibacterial activity against E. coli NCTC 10418, S. aureus NCTC 65710, P. aeruginosa NCTC 10662, B. subtilis MTCC 1133 and S. typhi MTCC 1253. The outcomes of anti-bacterial screening showed that among all the screened compounds, five compounds viz. 5b, 5c, 5f, 5k, and 5o showed moderate to good anti-bacterial activity having MIC values between 3.25-25 μg/mL. Three compounds of the series that is, 5a, 5d and 5e showed most promising antibacterial activity against E. coli NCTC 10418, S. aureus NCTC 65710, P. aeruginosa NCTC 10662, B. subtilis MTCC 1133 and S. typhi MTCC 1253 having MIC value 6.25 μg/mL. In addition, these three potential molecules were also studied for possible binding on penicillin binding protein by molecular docking and for druggable characteristics ADMET studies (PDB ID: 2Z2M).
Discovery of the first inhibitors of bacterial enzyme D-aspartate ligase from Enterococcus faecium (Aslfm)
?kedelj, Veronika,Perdih, Andrej,Brvar, Matja?,Krofli?, Ana,Dubbée, Vincent,Savage, Victoria,O'Neill, Alex J.,Solmajer, Tom,Be?ter-Roga?, Marija,Blanot, Didier,Hugonnet, Jean-Emmanuel,Magnet, Sophie,Arthur, Michel,Mainardi, Jean-Luc,Stojan, Jure,Zega, Anamarija
, p. 208 - 220 (2013/10/01)
The D-aspartate ligase of Enterococcus faecium (Aslfm) is an attractive target for the development of narrow-spectrum antibacterial agents that are active against multidrug-resistant E. faecium. Although there is currently little available information regarding the structural characteristics of Aslfm, we exploited the knowledge that this enzyme belongs to the ATP-grasp superfamily to target its ATP binding site. In the first design stage, we synthesized and screened a small library of known ATP-competitive inhibitors of ATP-grasp enzymes. A series of amino-oxazoles derived from bacterial biotin carboxylase inhibitors showed low micromolar activity. The most potent inhibitor compound 12, inhibits Aslfm with a Ki value of 2.9 μM. In the second design stage, a validated ligand-based pharmacophore modeling approach was used, taking the newly available inhibition data of an initial series of compounds into account. Experimental evaluation of the virtual screening hits identified two novel structural types of Aslfm inhibitors with 7-amino-9H-purine (18) and 7-amino-1H-pyrazolo[3,4-d]pyrimidine (30 and 34) scaffolds, and also with Ki values in the low micromolar range. Investigation the inhibitors modes of action confirmed that these compounds are competitive with respect to the ATP molecule. The binding of inhibitors to the target enzyme was also studied using isothermal titration calorimetry (ITC). Compounds 6, 12, 18, 30 and 34 represent the first inhibitors of Aslfm reported to date, and are an important step forward in combating infections due to E. faecium.
QUINOLONES USEFUL AS INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITORS
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Page/Page column 51, (2008/12/06)
The present invention relates to novel quinolones of Formula I that inhibit inducible NOS synthase together with methods of synthesizing and using the compounds including methods for inhibiting or modulating nitric oxide synthesis and/or lowering nitric oxide levels in a patient by administering the compounds for the treatment of disease.
