Docking of T6361 Analogues as Potential Inhibitors of MurA Followed by ADME-Toxicity Study.

Background: Developing more potent antibacterial agents is one of the most important tasks of scientists in the health field due to the problem of antibiotic resistance. Among the antibiotic targets, we mention MurA (UDP-N-Acetylglucosamine Enolpyruvyl Transferase), which is a key enzyme of peptidoglycan biosynthesis of the bacterial cell wall.

Objective: Our objective was to search for new inhibitors of the bacterial enzyme MurA by docking the analogues of its inhibitor T6361, a derivative of 5-sulfonoxy-anthranilic acid.

Investigation of New Inhibitors of UDP-N-Acetylglucosamine Enolpyruvyl Transferase (MurA) by Virtual Screening with Antibacterial Assessment.

Background: Considering the interesting role in the peptidoglycan biosynthesis pathway, the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase is an attractive target to develop new antibacterial agents. It catalyzes the first key step of this pathway and its inhibition leads to bacterial cell death. Fosfomycin is known as the natural inhibitor of MurA.

The Research of New Inhibitors of Bacterial Methionine Aminopeptidase by Structure Based Virtual Screening Approach of ZINC DATABASE and In Vitro Validation.

Background: The great emergence of multi-resistant bacterial strains and the low renewal of antibiotics molecules are leading human and veterinary medicine to certain therapeutic impasses. Therefore, there is an urgent need to find new therapeutic alternatives including new molecules in the current treatments of infectious diseases. Methionine aminopeptidase (MetAP) is a promising target for developing new antibiotics because it is essential for bacterial survival.

Identification of New Potent Acetylcholinesterase Inhibitors Using Virtual Screening and in vitro Approaches.

Acetylcholinesterase (AChE) is currently the most favorable target for the symptomatic treatment and reduction of Alzheimer's disease (AD). In order to identify new potent inhibitors of this enzyme, we describe herein a new structure-based virtual screening (SBVS) using the Institut Curie-CNRS chemical library (ICCL), which contained at the screening date 14307 compounds. The strategy undertaken in this work consisted of the use of several docking programs in SBVS calculations followed by the application of a consensus method (vSDC) and a scrupulous visual analysis.

Virtual Screening Approach of Bacterial Peptide Deformylase Inhibitors Results in New Antibiotics.

The increasing resistance of bacteria to antibacterial therapy poses an enormous health problem, it renders the development of new antibacterial agents with novel mechanism of action an urgent need. Peptide deformylase, a metalloenzyme which catalytically removes N-formyl group from N-terminal methionine of newly synthesized polypeptides, is an important target in antibacterial drug discovery. In this study, we report the structure-based virtual screening of ZINC database in order to discover potential hits as bacterial peptide deformylase enzyme inhibitors with more affinity as compared to GSK1322322, previously known inhibitor.

Theoretical study of Escherichia coli peptide deformylase inhibition by several drugs.

Because peptide deformylase (PDF) is essential for the initiation of translation in eubacteria but not in eukaryotes, it is a potentially interesting target for antibiotics. Computer simulation using docking software can be used to model protein-ligand interactions, and in this brief report we describe its use in optimizing the design in PDF-directed inhibitors. PDF was used as target for a set of five inhibitors with substantial structural differences.