Eva Sedlárová

Relationship between physicochemical properties, lipophilicity parameters, and local anesthetic activity of dibasic esters of phenylcarbamic acid

The basic physicochemical properties, lipophilicity parameters of dibasic alkyloxy-substituted phenylcarbamic acids were estimated. For the prepared set of compounds the experimentally obtained solubility, acidity, and lipophilicity parameters were correlated with those computed using various computer programs based on the associative artificial neural network and fragmental methods. The results of pharmacological evaluation were used as entry data for the complex correlations.

Synthesis, spectral description, and lipophilicity parameters determination of phenylcarbamic acid derivatives with integrated N-phenylpiperazine moiety in the structure

The phenylcarbamic acid derivatives with N-phenylpiperazine moiety in the molecule have been prepared. The structure has been confirmed by elemental analysis, IR, 1H NMR, and mass spectral data. For the prepared set of the compounds the lipophilicity parameters have been determined. The experimentally obtained lipophilicity parameters have been correlated with theoretical entries obtained by different computer programs based on the neural network and fragmental methods.

LACTASE IN IMMOBILIZED CELLS OF WATERMELON

A cell suspension culture of Citrullus vulgaris Schrad cv. “Samara” was permeabilized by Tween 80 and immobilized by glutaraldehyde. The highest lactase activity was achieved at pH 4.3, the temperature optimum for cell suspension was at 50°C, while for the immobilized cells the optimum was at 58°C. The hydrolysis of substrate was linear for 3 h, reaching 60-67% conversion rate. The cells were characterized by high enzyme activity. The stability of the enzyme showed convenient physico-mechanical properties (physical protection from shear forces and easy separation of product from biocatalysts) in long-term storage.

Permeability profiles of M-alkoxysubstituted pyrrolidinoethylesters of phenylcarbamic acid across caco-2 monolayers and human skin.

AbstractPurpose. The purpose of the present research was to study 10 m-alkoxysubstituted pyrrolidinoethylesters of phenylcarbamic acid—potential local anesthetics. The relationships between the structure of the molecule, its physicochemical parameters (log Doct, log k, RM, solubility) were correlated to the permeability data obtained from permeation experiments in Caco-2 monolayers and excised human skin in vitro. Methods. The extent and mechanism(s) of permeability of the series were studied through a Caco-2 monolayer in the apical-to-basolateral (a-b) and basolateral-to-apical (b-a) directions. The MTT test was performed to determine cellular damage. In vitro transdermal permeability data were obtained from permeation experiments on excised human skin by using side-by-side chambers. Passive diffusion and iontophoretically enhanced permeability were measured. Results. In Caco-2 monolayers, similar results in the shape of the permeability curves were obtained for the two directions. In the b-a direction, the values of Papp were ∼2-6 times greater than in the a-b direction. A plot of drug permeability vs. the number of carbons in the alkoxychain plateaued first, after which the permeability decreased by the increasing lipophilicity of the drug. If the log Doct of the ester was ≥ 3.4 and the MW > 385 Da, no measurable Caco-2 permeability was found. Cell damage was also higher by the more lipophilic compounds. In excised human skin, the relationship between the passive diffusion of the drugs and the number of carbons in the alkoxychain was parabolic (r2 = 0.95). Introducing low-level electrical current (iontophoresis), transdermal permeability of the more hydrophilic phenylcarbamic acid esters increased clearly. Conclusions. Lipophilicity and solubility of a compound have crucial roles in the permeation process. A very high lipophilicity has, however, a negative influence on the permeability, both intestinally and transdermally. Iontophoresis significantly increases the diffusion of small and less lipophilic compounds.