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 non-aromatic 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%.

Sustained release of a novel anti-quorum-sensing agent against oral fungal biofilms.

Thiazolidinedione-8 (S-8) has recently been identified as a potential anti-quorum-sensing/antibiofilm agent against bacteria and fungi. Based on these results, we investigated the possibility of incorporating S-8 in a sustained-release membrane (SRM) to increase its pharmaceutical potential against Candida albicans biofilm. We demonstrated that SRM containing S-8 inhibits fungal biofilm formation in a time-dependent manner for 72 h, due to prolonged release of S-8. Moreover, the SRM effectively delivered the agent in its active form to locations outside the membrane reservoir. In addition, eradication of mature biofilm by the SRM containing S-8 was also significant. Of note, S-8-containing SRM affected the characteristics of mature C. albicans biofilm, such as thickness, exopolysaccharide (EPS) production, and morphogenesis of fungal cells. The concept of using an antibiofilm agent with no antifungal activity incorporated into a sustained-release delivery system is new in medicine and dentistry. This concept of an SRM containing a quorum-sensing quencher with an antibiofilm effect could pave the way for combating oral fungal infectious diseases.

Synthesis and evaluation of thiazolidinedione and dioxazaborocane analogues as inhibitors of AI-2 quorum sensing in Vibrio harveyi.

Two focused libraries based on two types of compounds, that is, thiazolidinediones and dioxazaborocanes were designed. Structural resemblances can be found between thiazolidinediones and well-known furanone type quorum sensing (QS) inhibitors such as N-acylaminofuranones, and/or acyl-homoserine lactone signaling molecules, while dioxazaborocanes structurally resemble previously reported oxazaborolidine derivatives which antagonized autoinducer 2 (AI-2) binding to its receptor. Because of this, we hypothesized that these compounds could affect AI-2 QS in Vibrio harveyi. Although all compounds blocked QS, the thiazolidinediones were the most active AI-2 QS inhibitors, with EC(50) values in the low micromolar range. Their mechanism of inhibition was elucidated by measuring the effect on bioluminescence in a series of V. harveyi QS mutants and by DNA-binding assays with purified LuxR protein. The active compounds neither affected bioluminescence as such nor the production of AI-2. Instead, our results indicate that the thiazolidinediones blocked AI-2 QS in V. harveyi by decreasing the DNA-binding ability of LuxR. In addition, several dioxazaborocanes were found to block AI-2 QS by targeting LuxPQ.

Novel 3-hydroxy vinylboronates influence sphingolipid metabolism, cause apoptosis in Jurkat cells and prevent tumor development in nude mice.

A series of novel 3-hydroxy vinylboronates which share structural similarities with sphingolipids were synthesized and tested in vitro and in vivo as anticancer agents. The molecules reduced cancer cell survival in vitro by influencing their sphingolipid metabolism. In a cancer model in nude mice the lead compound E7 prevented the development of tumor as long as the treatment period continued. Moreover, it delayed tumor growth after the treatment was finished.

Mo(CO)6-mediated intramolecular Pauson-Khand reaction of substituted diethyl 3-allyloxy-1-propynylphosphonates.

Cyclisation of diethyl 3-allyloxy-1-propynylphosphonates with Mo(CO)(6) under PK conditions to give 3-substituted-5-oxo-3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4-ylphosphonate, 2a-h, in 45-88% isolated yields was done. The R groups are always syn with H(b) (where applicable). The stereochemistry was determined via both NMR and crystal X-ray analysis.

Synthesis of 3-hydroxy-1-alkenylboronates via phosphine stabilized borylzirconacyclopropenes.

Zirconacyclopropenylboronates can be stabilized to dimerization by complexation with tributylphosphine; the phosphine stabilized zirconacycle boronates react with aliphatic and aromatic ketones and aldehydes at C2 of the triple bond to give the previously unknown 3-hydroxyvinylboronates in 61-80% isolated yields.

Formation of diethyl 2-amino-1-cyclopentenylphosphonates: a simple synthesis with a unique mechanism.

Reaction of diethyl 5-chloro-1-pentynylphosphonate with primary and secondary amines produces novel 2-amino-1-cyclopentenylphosphonates, 1, in excellent isolated yields (79-88%). Calculations supported by experimental facts point to a two-step mechanism: an initial amine addition to give a zwitterionic intermediate followed by cyclization and proton transfer. Calculations rule out the formation of an enamine as an intermediate.

Recently synthesized class of vinylphosphonates as potent matrix metalloproteinase (MMP-2) inhibitors.

An in vitro evaluation of MMP-2 inhibitors for a series of novel vinylphosphonic acids and phosphonic esters that contain various functional groups, shows that various types exhibit excellent efficiency, and points towards potent, promising compounds. Other types displayed relatively weak activity.

Novel one-pot synthesis of 3-amino-1-alkenylphophonates by addition of imines to alkynylphosphonate titanium(II) complexes.

[reaction: see text] A new method of synthesis of 3-amino-1-alkenylphosphonates is described. It involves the addition of imines to the alkynylphosphonate titanium(II) complexes 2, which are prepared in situ from 1-alkynylphosphonates and Ti(O-i-Pr)(4)/2 equiv of i-PrMgCl. Compounds 4a-i were obtained regio- and stereoselectivily in high yields.