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Biomedical subjects

N Bodor

Publications and source records attributed to N Bodor.

195 records · Page 11Linked to original sources
PubMed1976

N-Halo derivatives V: Comparative antimicrobial activity of soft N-chloramine systems.

Comparative antimicrobial activity studies for certain new classes of soft N-chloramines derived from alpha-aminiisobutyric acid and 2-amino-2-methyl-1-propanol were examined using the minimum inhibitory concentration (MIC) and/or the contact germicidal efficiency (CGE) procedures. Several factors significantly aliphatic chain length in a homologous series, (b) the degree of chlorination of thenitrogen atom, (c) the solution pH, (d) the presence of a denaturant, and (e) the nature of a positive charge.

Anti-Infective Agents↗
PubMed1976

N-Halo derivatives VI: Microbiological and chemical evaluations of 3-chloro-2-oxazolidinones.

Comparative antimicrobial activity of 3-chloro-2-oxazolidinone (I), 3-chloro-4-methyl-2-oxazolidinone (II), 3-chloro-4,4-dimethyl-2-oxazolidinone (III), and N-chlorosuccinimide (IV) was evaluated in aqueous buffers in the absence and presence of 5% horse serum. All four compounds had similar bactericidal activity in the absence of horse serum, but I and III had superior activity relative to IV when serum was present. Compound III was considerably more stable with respect ot loss of positive chlorine and bactericidal activity than I and II when stored in 0.1 M sodium dihydrogen phosphate buffered to pH 7.0 at 40 degrees. Thus, III is potentially the most useful bactericidal agent of those evaluated. The chlorine potentials of I, II, and III, the rate constants for transfer of positive chlorine from I and III to morpholine in aqueous solutions, and the hydrolytic stabilities of I and III with respect to loss of positive chlorine were evaluated. These data, together with previously calculated data for IV, are used to rationalize the observed bactericidal activities.

Anti-Bacterial Agents↗
PubMed1976

Improved delivery through biological membranes. 1. Synthesis and properties of 1-methyl-1,6-dihydropyridine-2-carbaldoxime, a pro-drug of N-methylpyridinium-2-carbaldoxime chloride.

A dihydropyridine-pyridine type redox pro-drug system was developed for delivering quaternary pyridinium salts through biological membranes. As a first application, the dihydropyridine derivative of N-methylpyridinium-2-carbaldoxime chloride (2-PAM) was synthesized using a reduction-addition-elimination sequence. The dihydro-2-PAM obtained has all the required properties for an effective transport through lipoidal barriers and it reverts easily back to 2-PAM as a result of a chemical or enzymatic oxidation process.

Biological Transport↗
PubMed1976

Improved delivery through biological membranes. 2. Distribution, excretion, and metabolism of N-methyl-1,6-dihydropyridine-2-carbaldoxime hydrochloride, a pro-drug of N-methylpyridinium-2-carbaldoxime chloride.

N-Methyl-1,6-dihydropyridine-2-carbaldoxime hydrochloride, the pro-drug of 2-PAM, was found to be converted in vivo to 2-PAM, rapidly and quantitatively. The significantly changed properties of the pro-2-PAM resulted in a longer biological half-life and a favorable distribution of 2-PAM formed upon its oxidation. No new metabolite was found when pro-2-PAM was administered intravenously; however, a new metabolic product was formed when the pro-drug was given by oral route.

Administration, Oral↗
PubMed1976

Improved delivery through biological membranes. 3. Delivery of N-methylpyridinium-2-carbaldoxime chloride through the blood-brain barrier in its dihydropyridine pro-drug form.

Administration of N-methyl-1,6-dihydropyridine-2-carbaldoxime hydrochloride, the pro-drug form of 2-PAM, resulted in an average of 13-fold increase in the amount of 2-PAM delivered into the brain of mice as compared to the administration of 2-PAM. The pro-drug which crossed the BBB resulted in a dramatic increase in the reactivation of AChE blocked by DFP. In vivo studies of the "aging" of the phosphorylated AChE in the brain of mice could also be studied using pro-2-PAM.

Acetylcholinesterase↗
PubMed1975

Delivery of a quaternary pyridinium salt across the blood-brain barrier by its dihydropyridine derivative.

A dihydropyridine-pyridine type redox system was successfully applied for delivering a quaternary pyridinium salt, N-methylpyridinium-2-aldoxime chloride (2-PAM), through the blood-brain barrier. The dihydropyridine derivative of 2-PAM was quickly oxidized to 2-PAM after crossing the blood-brain barrier. As a result of this approach, the brain cholinesterase blocked by organophosphates could be reactivated. The new method should be useful in delivering numerous drugs which are otherwise inaccessible to the brain because of their polar ionic character.

Animals↗
PubMed1975

Rational development of a soluble prodrug of a cytotoxic nucleoside: preparation and properties of arabinosyladenine 5'-formate.

The 5'-O-formate ester of arabinosyladenine was synthesized and shown to be suitable as a water-soluble prodrug, being at least 60 times more soluble than the parent cytotoxic nucleoside. This increased solubility was ascribed to a decrease in intermolecular interaction in the crystalline state, as evidenced by an similar 90 degrees lower melting point for the ester relative to the parent compound. The prodrug reverted to the parent compound in aqueous solution, its pH-rate profile being V-shaped with maximum stability at a pH similar 4.2, corresponding to a half-life of about 10 days. The rate of hydrolysis of the prodrug at 37degrees in 91% human serum and 91% whole blood was studied. At an initial concentration of 0.4 mg of prodrug/ml of 91% whole blood, reversion to arabinosyladenine appeared to be essentially complete in about 15 min. The prodrug did not appear to be subject to enzymatic deamination. This feature, together with the good solubility of the prodrug, makes possible the effective formulation of arabinosyladenine for intravenous purposes. The rationale involved in the general design of a prodrug and the specific considerations necessitated in the case of adenine arabinoside are discussed.

Animals↗
PubMedDate not supplied

Development of a non-surfactant formulation for alfaxalone through the use of chemically-modified cyclodextrins.

The poor water solubility of alfaxalone (less than 5 micrograms/mL), a useful steroid anesthetic agent, was dramatically increased via complexation with a series of four cyclodextrins. The most effective agent was 2-hydroxypropyl-beta-cyclodextrin (2HPCD) which solubilized alfaxalone in a linear manner as a function of concentration. At a 2HPCD concentration of 50% w/v, approximately 80 mg/mL of alfaxalone was dissolved indicating an increase in aqueous solubility of over four orders of magnitude. The cyclodextrin solution was stable to autoclaving and could be conveniently lyophilized to yield a solid product.

Anesthetics↗
PubMedDate not supplied

The potential use of cyclodextrins in parenteral formulations.

The general use of cyclodextrins in drug formulations is reviewed. The ability of cyclodextrins to form reversible inclusion complexes with many drugs can eliminate various undesirable physicochemical properties. While beta-cyclodextrin is extremely useful in many of these applications, it is toxic when given parenterally, precluding its use in i.v. and other formulations. Chemically modified cyclodextrins such as 2-hydroxypropyl-beta-cyclodextrin are amorphous isomeric mixtures which are potent complexing agents and innocuous when administered i.e., either acutely or subchronically. The use of these modified cyclodextrins in parenteral formulations and to solubilize and stabilize various proteins and peptides is presented.

Chemical Phenomena↗
PubMedDate not supplied

Drug targeting via retrometabolic approaches.

Retrometabolic approaches incorporate targeting and metabolic considerations into the drug design process and represent a novel, systematic methodology for the design of safe, localized compounds. Two major design concepts aimed to increase the therapeutic index of drugs were developed. Chemical delivery systems allow targeting of active biological molecules to specific target sites or organs, based on predictable enzymatic activation. Soft drug approaches are used to design new drugs by building in the molecule, in addition to the activity, the most desired way in which the molecule is to be deactivated and detoxified subsequent to exerting its biological effects. Many examples are provided; related computer programs are also briefly discussed.

Animals↗