Quinazoline Derivatives Designed as Efflux Pump Inhibitors: Molecular Modeling and Spectroscopic Studies

Multidrug resistance of bacteria is a worrying concern in the therapeutic field and an alternative method to combat it is designing new efflux pump inhibitors (EPIs). This article presents a molecular study of two quinazoline derivatives, labelled BG1189 and BG1190, proposed as EPIs. In silico approach investigates the pharmacodynamic and pharmacokinetic profile of BG1189 and BG1190 quinazolines. Molecular docking and predicted ADMET features suggest that BG1189 and BG1190 may represent attractive candidates as antimicrobial drugs. UV-Vis absorption spectroscopy was employed to study the time stability of quinazoline solutions in water or in dimethyl sulfoxide (DMSO), in constant environmental conditions, and to determine the influence of usual storage temperature, normal room lighting and laser radiation (photostability) on samples stability. The effects of irradiation on BG1189 and BG1190 molecules were also assessed through Fourier-transform infrared (FTIR) spectroscopy. FTIR spectra showed that laser radiation breaks some chemical bonds affecting the substituents and the quinazoline radical of the compounds.     

Optimization of lantadenes isolation and preparation of 22 β-hydroxyoleanonic acid

The lantadenes fraction from Lantana camara was isolated and transformed to the medicinally important intermediate 22β-hydroxyoleanonic acid. The compound was studied for hepatotoxicity using lantadene A as standard and found to be nontoxic. Published in Khimiya Prirodnykh Soedinenii, No. 4, pp. 357–358, July–August, 2006.     

Cation transport by a redox-active synthetic ion channel

The synthesis, cation binding and transmembrane conductive properties of a novel group of synthetic ion channels containing a redox-active centre are described. Experiments using a black lipid membrane preparation revealed that these compounds function effectively as ion channels. Subsequent 23Na NMR spectroscopy studies focused on a synthesized ion channel with a ferrocene centre. When incorporated in vesicular bilayers, this channel was demonstrated to support a Na+ flux that was at least six times faster than ion transport by monensin. Since oxidation of the ferrocene moiety completely inhibited the Na+ transport, the redox-active centre provides a potential mechanism for controlling ion flux.     

Structural Changes of Cellulose Crystallites Induced by Mercerisation in Different Solvent Systems; Determined by Powder X-ray Diffraction Method

The completeness of mercerisation can be evaluated by investigating the changes in the crystalline regions of cellulose from cellulose I (C-I) to cellulose II (C-II) by the X-ray powder diffraction method. Mercerisation experiments in four different solution systems: ethanol/water, acetone, DMSO and xylene, are reported. Also the effect of some additives, external pressure, treatment time and alkalisation temperature were studied. In two-phase solvent systems, structural changes of cellulose crystallites depended primarily on the distribution and solubility of sodium hydroxide in the solvent phases. The sodium hydroxide concentration in the hydrophilic phase must exceed 7–8 w/w-% before complete crystal change from C-I to C-II can occur. The precipitation of sodium hydroxide due to high concentration prevents the successful use of one-phase ethanol/water system in slurry process. On the contrary, the 2-propanol/water/sodium hydroxide system separates into two layers; to the water-rich lower layer and the 2-propanol-rich upper layer, where the sodium hydroxide remains mainly in the water-rich lower layer. This prevents the precipitation of sodium hydroxide and promotes the alkalisation of cellulose. Ammonium chloride and ammonium hydroxide clearly had a positive effect by promoting the crystal changes, however, the urea concentration used in this study was obviously too small. In the advantageous two-phase 2-propanol/water systems, the alkalisation time was only 15 min when the treatment temperature was kept between 0 and 10 °C. Reduced external pressure was found to have a small but still detectable positive effect on cellulose alkalisation while over-pressure prevented crystal changes.     

A new ionic liquid dimethyldinonylammonium bromide as a flow modifier for the simultaneous determination of eight carboxylates by capillary electrophoresis

Two new methods of capillary zone electrophoresis based on aqueous phosphate running buffers with UV spectrophotometric detection were developed and optimized for the determination of eight carboxylates as copper complexes. Metalcomplexes are negatively charged, so measurements were made as anion analyses with flow reversal in the capillary. Two flow modifiers were used: a common tetradecyltrimethylammonium bromide (TTAB) and a new ionic liquid dimethyldinonylammonium bromide (DMDNAB). The methods were compared to each other. Better separation was achieved with DMDNAB as the flow modifier. Method development was done using a fused silica capillary (61 cm x 50 microm i.d.).Optimization was done using 95 mmol L(-1) phosphate buffer with TTAB or DMDNAB in the concentration 0.5 mmol L(-1) at pH 7.1. A -20 kV voltage and direct UV detection at 254 nm was used in measurements. In both CE methods all the peaks in the electropherograms were properly separated, the calibration plots gave good correlation coefficients and all eight carboxylates were detected in less than 7.5 min. The two methods were tested with natural water samples and a paper mill sample, and proved to be feasible.     

Convenient Method for the 3‐Functionalization of Isoindazoles

The C‐3 position of isoindazoles is readily functionalized by metalation with lithium diisopropylamide followed by reaction with a variety of electrophiles.     

Influence of β‐Cyclodextrin on the Mixed Micellization Process of Sodium Dodecyl Sulfate and Sodium Lauroyl Sarcosine and Formation of Inclusion Complexes

In this work, we have studied the influence of different concentrations of β‐Cyclodextrin (β‐CD) on the mixed micellization of anionic surfactants sodium dodecyl sulfate (SDS) and sodium lauroyl sarcosine (SLAS) at different SDS mole fractions (α_SDS). From conductivity data, the critical micellar concentration (cmc), the equivalent ionic conductivities of the monomeric species (Λ_m), the associated species (Λ_assc) and the micelle (Λ_mic), the degree of counterion dissociation (α) in the presence of β‐CD were evaluated from the slope of the conductivity versus concentration plots for the pure and binary mixtures. The apparent cmc of the surfactants vary linearly with the β‐CD concentrations. From the dependence of cmc of the surfactants on β‐CD concentration, we have deduced the association constant (K) of surfactant‐β‐CD inclusion complexes assuming 1∶1 stoichiometry. Theories of Clint, Regular solution, and Motomura's have been used for the evaluation of ideality or nonideality of the mixed system. Mixed micelles were found to be rich in SDS content at the cmc in the presence and the absence of β‐CD. The cmc values have been used to evaluate the transfer of standard free energy of micelles (ΔG⁰ _M,tr) from the aqueous medium to additive medium.     

Interactions of γ-Cyclodextrin with the Mixed Micelles of Anionic Surfactants and Their Inclusion Complexes Formation

Interactions of γ-cyclodextrin (γ-CD) with the single and mixed micelles of sodium dodecyl sulfate (SDS) and sodium lauroyl sarcosine (SLAS) have been studied at different concentrations of γ-CD by using conductivity measurements. From conductivity data, the pure and mixed critical micellar concentration (cmc), the equivalent ionic conductivities of the monomeric species (Λ _m), the associated species (Λ _assc) and the micelle (Λ _mic), the degree of counterion dissociation (χ) in the presence of γ-CD have been evaluated from the slope of the conductivity versus concentration plots for the pure and binary mixture of surfactants. From the dependence of cmc of the surfactantson γ-CD concentration, we have deduced the association constant (K) of surfactant-γ-CD inclusion complexes assuming 2:1 stoichiometry. Theories of Clint, regular solution, and Motomura's have been used for the evaluation of ideality or nonideality of the mixed system. Mixed micelles were found to be rich in SDS content in the presence and the absence of γ-CD. The cmc values have been used to evaluate the transfer of standard free energy of micelles (ΔG⁰ _M,tr) from the aqueous medium to additive medium.