ABSTRACT
The paper studies the adsorption of nine stobadin acylderivatives on active charcoal. Freundlich model of adsorption was employed to evaluate the course of adsorption in dependence on the concentration of substances. At the same time, the dependence of adsorption on lipophilicity and structural parameters of substances was evaluated. The dependence of the amount of the adsorbed substance on time served for the calculation of the rate constant of the 1st order of adsorption process. These values correlate with the parameters characterizing the size of the molecule.
Subject(s)
Carbolines/chemistry , Charcoal/chemistry , AdsorptionABSTRACT
The paper is concerned with the study of adsorption on active charcoal in a set of selected substances from the group of aryloxyaminopropanol derivatives with carbamate substitution on the benzene ring with beta-adrenolytic effect (Group A) and a set of substances, derivatives of [(arylcarbonyl)oxylaminopropanol with the identical, but assumed ultra-short effect (Group B), where the effect was produced by replacing the phenolether group with a metabolically unstable ester functional group. The course of adsorption in buffer solution with pH 7 in dependence on time and concentration is examined. Adsorptivity of substances is evaluated according to Freundlich and Langmuir models. Affinity of substances of Group A to adsorption material decreases with increasing hydrophilicity.
Subject(s)
Adrenergic beta-Antagonists/chemistry , Phenylcarbamates/chemistry , Adsorption , CharcoalABSTRACT
Active charcoal is one of important adsorbents capable of binding on their surface other substances in a relatively large amount. This property is often used in pharmacy as well as in the studies of the structure--biological activity relationships, where active charcoal serves as a model substance for the study of hyrophobic interactions. The present paper investigates the adsorptivity of eight potential local anaesthetics from the group of 1-methyl-2-piperidinoethylesters of 2-, 3- and 4-alkoxyphenylcarbamic acids to adjusted active charcoal, which complies with the requirements of Slovak Pharmacopoeia 1. Adsorptivity of substances is evaluated according to Freundlich model and according to the amount of the bound substance beta in per cents in dependence on time. The dependence of adsorptivity of substances beta on local anaesthetic activity in topical local anaesthesia, which increases with increasing lipophilicity, is evaluated.
Subject(s)
Anesthetics, Local , Charcoal , Phenylcarbamates , Adsorption , Chemistry, PharmaceuticalABSTRACT
The paper presents the results of an analytical evaluation and a study of some physicochemical properties of a new potential drug of the prodrug type--the substance BL 443 pivalate with an assumed antidysrhythmic effect. The structure of the substance has been confirmed by elemental analysis, IR and UV spectroscopy. The following parameters were determined: melting point, solubility, dissociation constant, experimental partition coefficient in four different systems, and surface activity. The chromatographic behaviour of the drug on a thin layer (adsorption and partition chromatography) was also investigated. Acidimetric titration in non-aqueous medium and spectrophotometry in the ultraviolet region of the spectrum at the wavelength of the second absorption maximum of the drug was employed to determine the content of the drug in pure substance.
Subject(s)
Anti-Arrhythmia Agents/chemistry , Prodrugs/chemistry , Valerates/chemistry , Chemical Phenomena , Chemistry, PhysicalABSTRACT
The pyridoindole derivative stobadin, [(-)-cis-2,8-dimetyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3b]-indole] is a perspective antiarrhythmic, antihistamine, anaesthetic, antiulcerous drug capable of extinguishing free oxygen radical. Its prodrug forms--N(5)- acyl-substituted stobadine--of the active substance--stobadine--have been prepared and it is assumed that the will be hydrolyzed in the organism and the active substance will be released in higher concentrations in different biological tissues. The present paper is concerned with the investigation of the kinetics of the hydrolysis of 13 acyl derivatives of stobadine in the medium of a buffer solution of pH 7 at temperatures of 70 degrees C and 75 degrees C spectrophotometrically in the UV region of the spectrum. The determined rate constants were correlated with the length of the side acyl chain and the pKa values of the drugs under study. The profile of log k--pH of substances was determined.
Subject(s)
Carbolines/chemistry , Free Radical Scavengers/chemistry , Prodrugs/chemistry , Hydrogen-Ion Concentration , HydrolysisABSTRACT
Stobadin, (-)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyridol[4,3b]- indol is a compound with a potential antiarrhythmic, antihistamine, anaesthetic, antiulcerous, and marked antioxidative effect. N5-acylsubstitution of stobadin yielded derivatives, which represent prodrug forms of the active principle--stobadin, and it is assumed that they will be hydrolysed in the organism and the active principle will be released in higher concentrations in various biological tissues. The present paper deals with the investigation of the kinetics of hydrolysis of 13 stobadin acylderivatives in a medium of 0.1 mol/l of sodium hydroxide at 70 degrees C, employing spectrophotometry in the UV region of the spectrum. The determined rate constants were correlated with the length of the side acyl chain and the pKa values of the compounds under study.
Subject(s)
Carbolines/chemistry , Free Radical Scavengers/chemistry , Prodrugs/chemistry , Hydrogen-Ion Concentration , Hydrolysis , Spectrophotometry, UltravioletABSTRACT
5'-Chloro-5'-deoxy arabinosylcytosine (Cl-araC) is a more lipophilic analog of the clinically used drug--arabinosylcytosine (araC). The resistance toward the enzyme cytidine-deaminase action was described as an characteristic feature of this synthetic nucleoside. The kinetics of the Cl-araC transformation in acid and alkaline solutions was studied at various temperatures. When compared with parent compound araC, the chlorine atom at the 5' position of the nucleoside sugar moiety increases the Cl-araC stability. The chlorine atom stabilizing effect is higher in acidic conditions. Cl-araC increased stability, antileukemic activity accompanied by higher lipophilicity confirm the fact that Cl-araC belong among interesting compounds from the point of view of cancer chemotherapy.
Subject(s)
Antineoplastic Agents/chemistry , Cytarabine/analogs & derivatives , Cytarabine/chemistry , Cytidine/chemistry , Cytosine/chemistry , Drug Stability , Hydrogen-Ion Concentration , Kinetics , Structure-Activity Relationship , ThermodynamicsABSTRACT
The present work deals with the kinetics of hydrolysis of the acyl derivatives of stobadine, an originally synthesized potential antiarrhythmic and antihypoxic drug, which was found to have also an excellent scavenging effect on reactive oxygen species. The acyl derivatives of stobadine, which possess high lipophilicity, represent model blood-brain barrier penetrating agents. It is assumed that the acyl derivatives of stobadine may act as prodrugs which are hydrolysed in different biological tissues to release the active drug. The decomposition of three acyl derivatives of stobadine was studied in acidic, basic and neutral buffer solutions at constant ionic strength (0.1 mol/L) at 25 degrees and 70 degrees C using UV spectrophotometric method. The pseudo first-order rate constants and the pH-rate profile for the degradation of acetyl-, valeroyl- and nicotinoyl-derivatives of stobadine were determined. Confirmation that stobadine was the first degradation product was provided by thin-layer chromatography.
Subject(s)
Anti-Arrhythmia Agents/chemistry , Antioxidants/chemistry , Carbolines/chemistry , Acetates/chemistry , Buffers , Chromatography, Thin Layer , Hydrogen-Ion Concentration , Hydrolysis , Kinetics , Nicotinic Acids/chemistry , Prodrugs/chemistry , Spectrophotometry, Ultraviolet , Valerates/chemistryABSTRACT
Hydrochloride of 5'-chloro-5'-deoxy-cyclocytidine (Cl-cC) is an analogue of cyclocytine hydrochloride (cC), a prodrug of the compound with the strong antileukemic activity arabinosylcytosine (araC). This paper is devoted to the study of its cytotoxic activity in vitro and to the effect of acid and alkaline conditions and temperature on its stability. Cl-cC inhibits not only the growth of L1210 leukemia cells in vitro and the DNA synthesis (IC50 = 0.09 mumol/l) but, at the same time, it has a weak effect on RNA synthesis (IC50 > 250 mumol/l) and no effect on proteosynthesis. In alkaline conditions Cl-cC is transformed to 5'-chloro-araC and 2',5'-anhydro-araC but is more stable in acid solutions.
Subject(s)
Ancitabine/pharmacology , Antimetabolites, Antineoplastic/pharmacology , Leukemia/drug therapy , Ancitabine/analogs & derivatives , Ancitabine/chemistry , Animals , DNA/biosynthesis , Drug Stability , Leukemia L1210/drug therapy , Leukemia L1210/pathology , Mice , Protein Biosynthesis , RNA/biosynthesis , Tumor Cells, CulturedABSTRACT
"Substance H + B", N-[2-(2-heptyloxyphenylcarbamoyloxy)-ethyl]-N- benzylpiperidine chloride (1) is a new potential antiarrhythmic, prepared by quarternization of the local anesthetic, antiarrhythmic and antimicrobial heptacaine, N-[2-(2-heptyloxyphenylcarbamoyloxy)-ethyl]-piperidine chloride. The content of the work was a study of the stability of 1 based on the short-time stability tests of aqueous solutions, the observation of long-time storing of the substance and study of the kinetics of hydrolysis in aqueous, ethanolic buffer solutions. The conclusions of the presented results are: 1 is stable in acidic and neutral media, the alkaline hydrolysis is faster from the start compared to the hydrolysis of heptacaine, but later obtains an equilibrium character.
Subject(s)
Anti-Arrhythmia Agents/chemistry , Piperidines/chemistry , Drug Stability , Hydrolysis , Kinetics , Solutions , TemperatureABSTRACT
The present paper has been focussed on the study of quantitative relations between structure, physico-chemical properties and biological activity in the series of substances with potential local anaesthetic and beta-adrenolytic effectiveness from the group of phenylcarbamic acid derivatives. The study of the above-mentioned relations and their interpretation could contribute to the optimization of new potential medicaments.
