Facile Synthesis of 2-Aminocyclobutenylphosphonates

The addition of various amines to diethyl 4-chlorobut-1-yn-1-ylphosphonate produced novel biologically potent substituted diethyl 2-aminocyclobut-1-en-1-ylphosphonates in 70–83% isolated yield. This regioselective reaction was carried out at room temperature in the absence of solvent and catalyst

Oxetane-containing metabolites: origin, structures, and biological activities

Cyclobutanes containing one oxygen atom in a molecule are called oxetane-containing compounds (OCC). More than 600 different OCC are found in nature; they are produced by microorganisms, and also found in marine invertebrates and algae. The greatest number of them is found in plants belonging to the genus Taxus. Oxetanes are high-energy oxygen-containing nonaromatic heterocycles that are of great interest as new potential pharmacophores with a significant spectrum of biological activities. The biological activity of OCC that is produced by bacteria and Actinomycetes demonstrates antineoplastic, antiviral (arbovirus), and antifungal activity with confidence an angiogenesis stimulator, respiratory analeptic, and antiallergic activity dominate with confidence from 81 to 99%

An Aminopyrrolidinyl Phosphonates—A New Class of Antibiotics: Facile Synthesis and Predicted Biological Activity

A novel class of aminopyrrolidinyl phosphonates was synthesized in 74% - 80% isolated yield by the addition of three-fold excess of primary amines to diethyl 4-chloro-1-butynylphosphonates. The reaction was carried out at room temperature and in the absence of solvent or catalyst to give solely compounds which showed predicted biological activity based on PASS program. Some of the synthesized derivatives of antibiotics exhibit properties for the treatment of stroke, the treatment of acute neurological disorders, and can also be acetyl esterase inhibitors

Mechanistic analysis of a synthetic inhibitor of the LasI quorum-sensing signal synthase

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen responsible for many human infections. LasI is an acyl-homoserine lactone synthase that produces a quorum-sensing (QS) signal that positively regulates numerous P. aeruginosa virulence determinants. The inhibition of the LasI protein is therefore an attractive drug target. In this study, a novel in silico to in vitro complementation was applied to screen thiazolidinedione-type compounds for their ability to inhibit biofilm formation at concentrations not affecting bacterial growth. The compound (z)-5-octylidenethiazolidine-2, 4-dione (TZD-C8) was a strong inhibitor of biofilm formation and chosen for further study. Structural exploration of in silico docking predicted that the compound had high affinity for the LasI activity pocket. The TZD-C8 compound was also predicted to create hydrogen bonds with residues Arg30 and Ile107. Site-directed mutagenesis (SDM) of these two sites demonstrated that TZD-C8 inhibition was abolished in the lasI double mutant PAO-R30D, I107S. In addition, in vitro swarming motility and quorum sensing signal production were affected by TZD-C 8, confirming this compound alters the cell to cell signalling circuitry. Overall, this novel inhibitor of P. aeruginosa quorum sensing shows great promise and validates our mechanistic approach to discovering inhibitors of LuxI-type acyl-homoserine lactone synthases

Excavations at Tell Brak 2006-2007

have offprint FranceNational audienc