To counteract bacterial resistance, we investigated the interruption of quorum sensing mediated by non-classical bioisosteres of the N-hexanoyl homoserine lactone with an azoline core. For this purpose, a set of selected 2-substituted azolines was synthesized, establishing the basis for a new protocol to synthesize 2-amino imidazolines. The synthesized compounds were evaluated as inhibitors of violacein production in Chromobacterium violaceum. Theoretical studies on bioisostere-protein interactions were performed using CviR. The results show that some azolines decreased violacein production, suggesting an antiquorum sensing profile against Gram-negative bacteria. Docking and molecular dynamic simulations together with binding free energy calculations revealed the exact binding and inhibitory profiles. These theoretical results show relationship with the in vitro activity of the azoline series.

Films modified with SA for 13.5 h adsorb more than four times the amount of APTAC C compared to the unmodified films (Fig. 4). It is also noteworthy that the time for reaching the plateau region increases with the length of the reaction time ( Table 2). When the number of layers is increased to 100 and the film is treated with SA for 13.5 h, the system adsorbs more than 18.7 mg/m2 and reaches the plateau level after two hours (Table 2). In the case of the thicker films, one should consider that the modification could also occur in deeper layers and that the polyelectrolyte could not only adsorb on the surface but also penetrate into the modified multilayer Preliminary investigations on the influence of salts and an additional polyelectrolyte have shown that it is possible to detect double-adsorption processes. Following this concept a simulation of a two-component retention system consisting of a combination of anionic and cationic polymers should be possible."*]The cases presented here confirm that cellulose films obtained from the regeneration of TMSC LB films provide a model system for adsorption studies. The adsorption processes of dyes and polyelectrolytes can be followed by means of SPR using a flow system. The cellulose films have several advantages compared to cellulose fibers as an adsorption substrate since problems arising from the porous topology of cellulose fibers do not appear. Furthermore, the orientation of the chain axes within the surface of an altogether perfectly defined system of layered texture is advantageous in comparison to disordered films like Cellophan. The derivatization with succinic anhydride is one possibility for changing the chemical properties of the cellulose films. Subsequent chemical modifications of the multilayer systems should be generalizable to convenient methods for introducing desired surface properties. ExperimentalTMSC was synthesized according to a procedure described elsewhere [18]; the polymer used in this work had a DP of 150 (degree of polymerization, number averaged) and a DS of 2.73 (degree of substitution). TMSC was spread from a solution of 4 mg polymer in 10 ml n-hexan and transferred following the given conditions [3,4]. Except for the SPR measurements, TMSC was deposited on silicon wafers (Wacker) that were hydrophobized with ammonium fluoride etchant (Selectipur, Merck). For the SPR experiments glass slides were used that had a refractive index of n = 1.847 (Moeller J. D. Optische Werke) and were covered with 20 A chromium and 450 A gold (Bakers).The regeneration was carried out according to the method described by Schaub [3,4]. In order to perform the esterification, the regenerated multilayer systems deposited on the appropriate substrate were incubated in a 0.22 mol/l solution of succinic anhydride in DMF / CHzClz (1:20) at room temperature for the desired time. The films were then thoroughly washed with water and incubated with CH3CN/Hz0 (1:l) for 20 min. This washing procedure was repeated five times, and after incubating the films with water for 3...

Aflatoxin B 1 is a contaminant of agricultural and dairy products that can be related to mutagenic and carcinogenic effects. In this report we explore the capacity of α-mannan (Man) to reduce the DNA damage induced by AFB 1 in mouse hepatocytes. For this purpose we applied the comet assay to groups of animals which were first administered Man (100, 400 and 700 mg/kg, respectively) and 20 min later 1.0 mg/kg of AFB 1 . Liver cells were obtained at 4, 10, and 16 h after the chemical administration and examined. The results showed no protection of the damage induced by AFB 1 with the low dose of the polysaccharide, but they did reveal antigenotoxic activity exerted by the two high doses. In addition, we induced a co-crystallization between both compounds, determined their fusion points and analyzed the molecules by UV spectroscopy. The obtained data suggested the formation of a supramolecular complex between AFB 1 and Man. OPEN ACCESSInt. J. Mol. Sci. 2009, 10 396

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A series of selected 2-substituted imidazolines were synthesized in moderate to excellent yields by a modification of protocols reported in the literature. They were evaluated as potential non-classical bioisosteres of AHL with the aim of counteracting bacterial pathogenicity. Imidazolines 18a, 18e and 18f at various concentrations reduced the violacein production by Chromobacterium violaceum, suggesting an anti-quorum sensing profile against Gram-negative bacteria. Imidazoline 18b did not affect the production of violacein, but had a bacteriostatic effect at 100 μM and a bactericidal effect at 1 mM. Imidazoline 18a bearing a hexyl phenoxy moiety was the most active compound of the series, rendering a 72% inhibitory effect of quorum sensing at 100 μM. Imidazoline 18f bearing a phenyl nonamide substituent presented an inhibitory effect on quorum sensing at a very low concentration (1 nM), with a reduction percentage of 28%. This compound showed an irregular performance, decreasing inhibition at concentrations higher than 10 μM, until reaching 100 μM, at which concentration it increased the inhibitory effect with a 49% reduction percentage. When evaluated on Serratia marcescens, compound 18f inhibited the production of prodigiosin by 40% at 100 μM.