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Biomedical subjects

S Baláz

Publications and source records attributed to S Baláz.

18 recordsLinked to original sources
PubMed1992

alpha-Amylases and approaches leading to their enhanced stability.

The recent state of the knowledge of properties and structure of alpha-amylases is reviewed with the aim of elucidation the basis for their stabilization. Three principal ways for obtaining stable alpha-amylases (isolation of enzymes from extremophiles, production of extremophilic enzymes in mesophiles, and modification of mesophilic enzymes) are discussed separately. Detailed experimental examples are given for modification approaches.

Enzyme Stability↗
PubMed1992

A time hierarchy-based model for kinetics of drug disposition and its use in quantitative structure-activity relationships.

By using the time hierarchy of the processes determining the fate of drugs in biosystems (absorption, transport, distribution, protein binding, and elimination), a one-compartment open model is formulated at a subcellular level for the disposition phase of pharmacokinetics. The resulting disposition function describes the kinetics of the intracellular disposition of drugs as determined by their hydrophobicity, acidity or basicity, affinity to proteins, and rate parameters of elimination. Structure-activity relationships, based on the function with incorporated extrathermodynamic relations, fit the literature data well (fixed-time bioactivity-hydrophobicity profiles, kinetics of microbial degradation of organic compounds, and kinetics of analgesic effects of fentanyl derivatives in rats). Application of the approach, creating a basis for the construction of model-based quantitative structure-time-activity relationship, to biosystems of varying complexity is discussed.

Animals↗
PubMed1991

A kinetic description of the fate of chemicals in biosystems.

A simple kinetic description of the fate of low-molecular-weight compounds in biosystems was derived using the mass action law. Michaelis-Menten kinetics of enzymatic reactions was considered with respect to its two boundary cases, namely first- and zero-order kinetics. Absorption, membrane accumulation, non-covalent protein binding, biotransformation, and excretion have been included in the model, with only the last two steps being considered as time-dependent on the pertinent time scale of hours and days. This time hierarchy allowed for simplification of the resulting expression. In accordance with the results of uptake experiments and contrary to previous approaches, transport of organic molecules into the cell was not considered as the rate-limiting step. The decisive compound properties were found to be hydrophobicity and the intrinsic rate parameters of biotransformation and excretion. The model was applied to the elucidation of the dependence of the observed biotransformation rate parameters on hydrophobicity. The resulting equations are consistent with literature data.

Biotransformation↗
PubMed1988

Kinetics of drug activities as influenced by their physico-chemical properties: antibacterial effects of alkylating 2-furylethylenes.

A method is presented allowing for direct incorporation of the time of exposure into the relationship between biological and physico-chemical properties of drugs. The approach employs kinetics of the drug-receptor interaction based on mass action law, whereby biological response is considered as proportional to the receptor modification, and the time-dependent drug concentration in the vicinity of receptors is expressed by a disposition function. The function with variable physico-chemical properties and time relates the intracellular drug concentration to the dose. General description of individual steps in the development of a quantitative structure-time-activity relationship (QSTAR) is illustrated in detail using the data on antibacterial effects of alkylating 2-furylethylenes. It is shown that common approaches to description of quantitative structure-activity relationships (QSAR), working with a prefixed time of exposure, represent special cases of the method presented and can even be improved using its conclusions.

Bacteria↗
PubMed1988

Liposome/saline partition coefficients of low-molecular-weight solutes by gel chromatography.

A chromatographic method for the determination of association constants of rapidly dissociable complexes is described and applied to quantification of liposome/saline partition coefficients using gel chromatography. The approach allows for estimation of the free solute concentration in the sample by simple manual processing of the intact right-hand part of the solute peak deformed due to gradual diffusion of the accumulated solute from the liposomes along the separation column. Validity of the procedure was confirmed by both reasonable agreement with equilibrium dialysis data and model-based deconvolution of the distorted peak into its two components corresponding to initially unbound compound and to that escaped from the liposomes during the separation process.

Chromatography, Gel↗
PubMed1987

Model-based relationship between physicochemical properties and inhibitory potency of alkylating 2-furylethylenes on yeast glycolysis.

Inhibitory effects of 35 2-furylethylenes, non-specific alkylating agents, on glycolysis in a respiratory mutant of Saccharomyces cerevisiae were correlated with their 1-octanol/water partition coefficients and the rate constants for reaction with 2-mercaptoacetic acid using physiologically based models. The simplest model explaining the data satisfactorily consists of two-step drug-receptor interaction involving reversible formation of a structurally non-specific non-covalent complex stabilized later covalently. The concentration of the free drug in the receptor surroundings was related to its initial concentration in external medium via a simple form of a disposition function constructed on the basis of time hierarchy of passive membrane transport, non-covalent binding to cell constituents and metabolic inactivation of the drug.

Alkylating Agents↗
PubMed1987

Kinetics of non-equilibrium metabolism-coupled passive transport in biosystems.

Expressions for time course of solute concentration in an arbitrary compartment of a biosystem were derived using simplifying assumptions of unidirectional transport and first order metabolism kinetics. The coefficients of the resulting exponential-summation function comprise, in addition to the volumes and the connecting areas of individual compartments, the rate parameters of the processes mentioned. The equations presented were verified using results obtained in drug potency testing.

Biological Transport↗
PubMed1986

Quantitative structure-activity relationship of carbonylcyanide phenylhydrazones as uncouplers of mitochondrial oxidative phosphorylation.

The dependence of the uncoupling activity in the series of 16 carbonylcyanide phenylhydrazones on their physico-chemical properties (partition coefficient, dissociation constant and rate constant for reaction with thiols) is investigated using two physiologically based models, one for protonophoric mechanism of uncoupling and the other assuming the covalent modification of a membrane constituent to be the key step in this process. As indicated by uptake experiments, at the given conditions a lipophilic-hydrophilic equilibrium is attained without any loss of the compounds via chemical reactions. Using this fact to reduce the number of adjustable parameters, a better fit to the data on stimulation of respiration is obtained with the former (protonophoric) model.

Animals↗
PubMed1986

Kinetics of unidirectional transport in multimembrane systems as influenced by binding to macromolecules.

The distribution of externally added low-molecular-weight solutes in systems comprising alternating membraneous and aqueous compartments with binding capacity is described for special conditions of unidirectional transport and linear (i.e., far from saturation) binding. The kinetics of the process valid for a certain time period is expressed as the sum of exponential functions of time, their number being equal to the number of compartments investigated. The coefficients of the equation involve the rate and equilibrium parameters of the process as well as the volumes and the connecting areas of individual compartments. The degenerated case resulting from the cellular structure of biosystems is also considered. The description is shown to agree well with the results of drug potency testing, bioactivity being used to monitor concentration of an effector in the receptor region.

Analgesia↗
PubMed1986

Relationships between structure of 5-nitro-2-furylethylenes and their SOS-function-inducing activities in Escherichia coli.

The SOS-function-inducing activities of 36 furylethylenes were characterized in Escherichia coli K12. The induction of the SOS function was assayed by monitoring the beta-galactosidase activity in the sulA::lacZ fusion strain PQ 37. To correct for the inhibitory effects of test compounds on mRNA or protein synthesis, the level of the constitutive alkaline phosphatase was assayed in parallel. Tested furylethylenes included nine alkylesters and eleven N-alkylamides of 5-nitro-2-furylacrylic acid (NFAA) and fourteen derivatives differing not only in substituents at exocyclic double bond, but also in the position 5 of the furan ring. The induction of the SOS-function by the derivatives depends on the presence of 5-nitrofuran centre in their molecule; side chains in the position 2 modify the degree of SOS response. SOS-inducing potency of n-alkyl congeners decreases with increasing lipophilicity. Effect of derivatives with branched alkyl substituents is lower than expected from the behavior of the n-alkyl homologues. All derivatives with positive effect on SOS-function in E. coli show mutagenic activity on Salmonella typhimurium TA98 in Ames test.

Acrylates↗
PubMed1985

Antimicrobial activity of methyl esters and nitriles of 2-cyano-3-(5'-R-2'-furyl)propenic acid.

Derivatives of 2-cyano-3-(2'-furyl)propenic acid with a markedly polarized double bond inhibit the growth of Chlorella pyrenoidosa, Saccharomyces cerevisiae, Candida albicans and Aspergillus niger at concentrations above 40 mumol/L. Their antibacterial activity (Escherichia coli B, Bacillus subtilis) is low. The biological effect increases with an increasing electron acceptor effect and decreasing hydrophobicity of the substituent on the furan ring. Substitution of methoxycarbony] group with cyano group in position 1 slightly increases the biological activity.

Anti-Bacterial Agents↗
PubMed1985

Quantitative relationships between lipophilicity and mutagenic effects of N-substituted amides of 3-(5-nitro-2-furyl)-acrylic acid on Salmonella typhimurium.

Mutagenic effects of 10 N-alkylamides of 3-(5-nitro-2-furyl)-acrylic acid were assessed in two strains of Salmonella typhimurium TA100 (rfa+ and rfa-). Experimental data were confronted with physiologically based compartment model comprising passive membrane transport, metabolical inactivation in cytoplasm and formation of a reactive intermediate which is responsible for receptor modification. The quantitative dependences observed between mutagenicity and lipophilicity indicate that, in both cases, the drug-receptor interaction takes place in a hydrophobic compartment localized in the cytoplasm. The mutagenic potency of some derivatives was influenced also by stericity.

Acrylates↗
PubMedDate not supplied

Structure-mutagenicity relationships of 5-nitro-2-furylethylenes in Salmonella typhimurium TA98.

Mutagenicity of three selected series of 2-furylethylene was determined by the Ames test. These included: nine alkylesters and eleven N-alkylamides of 5-nitro-2-furylacrylic acid (NFAA) and ten derivatives differing not only at exocyclic double bond, but also in the position 5 of the furan ring. Mutagenicity of the derivatives depends on the presence of the 5-nitro-furan centre in the molecule; side chains in the position 2 modify the degree of mutagenicity. Among the derivatives of NFAA tested as changing the substituents virtually does not affect chemical properties of the 5-nitrofuran ring. Mutagenicity of the n-alkyl congeners decreases linearly with increasing lipophilicity. Mutagenicity of the derivatives with branched alkyl substituents is lower than expected from the behaviour of the n-alkyl homologues.

Acrylates↗