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Background: View to its 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 the bacterial cell death. Fosfomycin is known as the natural inhibitor of MurA. Objective: Call new inhibitors of MurA by virtual screening of different chemical compounds libraries, and test the best scored “virtual hits” against three pathogenic bacteria: Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. Methods: A Virtual screening of the structural analogues of fosfomycin downloaded from PubChem database was performed on one side and of the French National Chemical Library as well as using ZINC database to identify new structures different from fosfomycin on the other, FlexX was the software used for this study. The antibacterial testing was divided into methods: disk diffusion and broth dilution. Results: A set of virtual hits was found with better energy score than that of fosfomycin, seven between them were tested in vitro. Therefore, disk diffusion method explored four compounds exhibited antibacterial activity: CID-21680357 (fosfomycin analogue), AB-00005001, ZINC04658565, and ZINC901335. The testing was continued by broth dilution method for both compounds CID-21680357 and ZINC901335 to determine their minimum inhibitory concentrations, and ZINC901335 had the best value with 457µg/ml against Staphylococcus aureus. Conclusion: Four compounds were found and proven in silico and in vitro to have antibacterial activity: CID-21680357, AB-00005001, ZINC04658565, and ZINC901335.

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. It allowed us to obtain a high degree of success, with a yield of almost 86 %, since 12 hits were identified among only 14 molecules tested in vitro. Still more remarkably, 6 of these hits were more active than galantamine, the reference inhibitor. These hits were predicted to have good ADMET properties. The two most promising compounds can serve as leads for AD treatment.

− Alzheimer's disease is a chronic neurodegenerative disorder with no curative treatment. The commercially available drugs, which target acetylcholinesterase, are not satisfactory. The aim of this study was to investigate the cholinesterase inhibitory activity of Solenostemma argel aerial part. Eight compounds were isolated and identified by NMR: kaempferol-3-O-glucopyranoside (1), kaempferol (2), kaempferol-3-glucopyranosyl(1→6)rhamnopyranose (3) p-hydroxybenzoic acid (4), dehydrovomifoliol (5), 14,15-dihydroxypregn-4-ene-3,20-dione (6), 14,15-dihydroxy-pregn-4-ene-3,20-dione-15β-D-glucopyranoside (7) and solargin I (8). Two of them (compounds 2 and 3) could inhibit over 50 % of butyrylcholinesterase activity at 100 µM. Compound (2) displayed the highest inhibitory effect against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with a slight selectivity towards the latter. Molecular docking studies supported the in vitro results and revealed that (2) had made several hydrogen and π-π stacking interactions which could explain the compound potency to inhibit AChE and BChE.

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