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Biomedical subjects

N Bodor

Publications and source records attributed to N Bodor.

At least 181 records · Page 10Linked to original sources
PubMed1983

Improved delivery through biological membranes. 13. Brain-specific delivery of dopamine with a dihydropyridine in equilibrium with pyridinium salt type redox delivery system.

The dihydropyridine in equilibrium with pyridinium salt type redox delivery system was used for the brain-specific delivery of dopamine. In vivo administration of the catechol-protected dopamine coupled with 1,4-dihydrotrigonelline as the carrier resulted in brain-specific, high and sustained concentrations of the 1-methyl-3-[N-[beta-(3,4-dihydroxyphenyl)ethyl]carbamoyl]pyridinium salt, the direct dopamine precursor, locked in the brain for many hours, while systemic concentration decreased fast, with a t 1/2 of less than 30 min. Significant dopaminergic activity was observed in the brain, which was sustained for hours.

Animals↗
PubMed1982

Soft drugs V: Thiazolidine-type derivatives of progesterone and testosterone.

Progesterone and testosterone are natural soft drugs, but to be used as drugs, their fast and facile metabolism must be prevented and their delivery controlled. A prodrug-soft drug combination can serve this purpose. Thiazolidines of testosterone, testosterone 17-propionate and progesterone were synthesized from the reaction of cysteine alkyl esters, N-methylaminoethanethiol, and mercaptamine and their hydrochlorides with the appropriate steroids. The thiazolidines function as bioreversible derivatives of the parent steroids.

Animals↗
PubMed1981

Site-specific, sustained release of drugs to the brain.

A dihydropyridine-pyridinium salt type of redox system is used in a general and flexible method for the site-specific or sustained delivery (or both) of drugs to the brain. A biologically active compound linked to a lipoidal dihydropyridine carrier easily penetrates the blood-brain barrier. Oxidation of the carrier part in vivo to the ionic pyridinium salt prevents its elimination from the brain, while elimination from the general circulation is accelerated. Subsequent cleavage of the quaternary carrier-drug species results in sustained delivery of the drug in the brain and facile elimination of the carrier part.

Animals↗
PubMed1981

Improved delivery through biological membranes VIII: Design, synthesis, and in vivo testing of true prodrugs of aspirin.

Novel activated ester-type prodrugs of aspirin were designed and synthesized. The methylthiomethyl, methylsulfinymethyl, and methylsulfonylmethyl esters of aspirin (acetylsalicylic acid) were cleaved in vitro in plasma to form aspirin rather than the corresponding salicylates. In vitro studies using dogs indicated that at least one aspirin derivative, methylsulfinylmethyl-2-acetoxybenzoate, is a true aspirin prodrug since aspirin was detected in the blood after prodrug administration.

Animals↗
PubMed1981

Improved delivery through biological membranes IX: Kinetics and mechanism of hydrolysis of methylsulfinymethyl 2-acetoxybenzoate and related aspirin prodrugs.

The complex kinetics and mechanism of the hydrolysis of the methylthiomethyl, methylsulfinylmethyl, and methylsulfonylmethyl 2-acetoxybenzoates, novel aspirin prodrugs, were studied. The pH profiles for the related salicylates and benzoates also were determined. Based on the activation parameters, isotope effects, and other data, it was established that the methylthiomethyl esters hydrolyze via a unimolecular alkyl-oxygen cleavage. The methylsulfinylmethyl and methylsulfonylmethyl 2-acetoxybenzoates undergo neutral hydrolysis of esters at pH greater than 4 to form aspirin, while water acts as a general base; but at lower pH, a different mechanism takes place and the o-acetyl group cleaves first, releasing the corresponding salicylates.

Aspirin↗
PubMed1981

Improved delivery through biological membranes XD: Percutaneous absorption and metabolism of methylsulfinylmethyl 2-acetoxybenzoate and related aspirin prodrugs.

Oxidative-reductive interconversion of the methylthiomethyl ester of aspirin and the corresponding sulfoxide and sulfone derivatives can be detected in rat liver homogenate, in addition to the extremely facile hydrolysis of these esters. The methylthiomethyl and methylsulfinylmethyl 2-acetoxybenzoates penetrate freshly excised hairless mice skin rather easily with the simultaneous hydrolysis of the two ester functions. Contrary to in vivo observations in dogs, where significant amounts of aspirin formed, the prodrugs cleave to salicylic acid and/or salicylate esters rather than aspirin.

Animals↗
PubMed1980

Antimicrobial activity of N-chloramine compounds.

Cellular mechanisms of action of two representative N-chloramines were studied. Both compounds, 3-chloro-4,4-dimethyl-2-oxazolidinone (I) and N-chlorosuccinimide (III), inhibited bacterial growth and exerted profound inhibition of bacterial DNA, RNA, and protein synthesis at a concentration of 10(-5) M. Enzymes containing sulfhydryl groups generally were significantly inhibited by these chloramines at 10(-4) M. Dihydrofolate reductase, which contains no sulfhydryl groups, also was inhibited but at much higher chloramine concentrations (10(-2) M); ribonuclease, which also contains no sulfhydryl groups, was unaffected. All of these inhibitory effects of the chloramines could be prevented if sulfhydryl-containing reagents (mercaptoethanol or dithiothreitol) were added before or together with the chloramine. Once inhibition was produced by the chloramine, it was not reversible by later addition of the sulfhydryl reagents. These results suggest that these chloramines act at sulfhydryl sites as well as at other sites in both cells and purified enzymes.

Anti-Bacterial Agents↗
PubMed1980

Soft drugs. 1. Labile quaternary ammonium salts as soft antimicrobials.

Strategies for the design of safer drugs are discussed. The various classes of "soft drugs" are designed to avoid undesired metabolic disposition (primarily various oxidative routes, occurring via possible toxic intermediates) and to be metabolized by a predictable manner with controlled rates. As a first example for the "soft analogue" type drugs, a new class of antimicrobial, surface-active quaternary salts of the type RCOOCHR1--N+ comes from X- was developed. These "soft" quaternary salts are isosteric analogues of known "hard" quaternary surfactants and are characterized by predictable and controllable cleavage (metabolism) to nontoxic components, while showing good activity against a wide range of bacteria. Due to their soft nature (low toxicity), the new antimicrobials are much safer than the conventional, hard analogues.

Anti-Bacterial Agents↗
PubMed1980

Soft drugs. 3. A new class of anticholinergic agents.

A new class of antimuscarinic drugs was designed and synthesized. The compounds are "soft" quaternary ammonium esters in which there is only one carbon atom separating the ester oxygen and the quaternary head. The compounds are potent anticholinergics when derived from hindered "umbrella" acids and cholinergics when derivatives of simple aliphatic acids. The more potent anticholinergics have up to 10 times higher acetylcholine antagonist activity than atropine, but they have a much shorter duration of action. The compounds cleave hydrolytically with simultaneous destruction of the quaternary head. The compounds are promising as selective, local agents, particularly as inhibitors of eccrine sweating.

Acetylcholine↗
PubMed1980

Soft drugs. 2. Soft alkylating compounds as potential antitumor agents.

A class of soft alkylating compounds as potential anticancer agents was developed. The first examples include alpha-halo esters of various carboxylic acids. A new method for quantitative evaluation of the alkylating reactivity was developed, using a competitive alkylation reactivity was developed, using a competitive alkylation reaction, followed by NMR analysis of the reaction mixture. The method is sensitive and reproducible. One of the two selected soft alkylating agents, chloromethyl hexanoate, was found to have anticancer activity.

Alkylating Agents↗
PubMed1978

Elimination of a quaternary pyridinium salt delivered as its dihydropyridine derivative from brain of mice.

1-Methylpyridine-2-carbaldehyde oxime, a quaternary pyridinium salt, can be delivered efficiently through the blood-brain barrier in its dihydropyridine prodrug form. This redox system was used to study the elimination rate from the brain of a small quaternary salt. It was found that the oxime is eliminated relatively fast from the brain, which supports a hypothesis for the existence of an active transport mechanism for eliminating organic ions from the brain. The possibilities of using the pyridinium salt in equilibrium dihydropyridine redox system for specific delivery of drugs to the brain are discussed.

Animals↗
PubMed1978

Controlled delivery of theophylline: chemistry of 7-acyl- and 7,7'-acylditheophylline derivates.

7-Acyl- and 7,7'-acylditheophylline derivatives were prepared from the reaction of theophylline with acid chlorides. In addition, a novel synthesis of these compounds was developed, which proceeds through an acylonium ion generated under mild conditions. The physical properties and stability of the derivative of choice, 7,7'-succinylditheophylline, depend on the synthetic procedure employed. This compound is a useful controlled-release prodrug of theophylline.

Animals↗
PubMed1978

Electronic structures of some antimicrobial N-chloramines. Possible existence of intramolecular hydrogen bonding and its effect on germicidal efficiency.

The photoelectron spectra of eight N-chloramines and N,N-dichloramines derived from either alpha-aminoisobutyric acid or 2-amino-2-methylpropanol have been measured. The lone-pair ionization potentials obtained from the photoelectron spectra have been interpreted to indicate that a substantial intramolecular interaction exists between tne N-H function and the various oxygen lone pairs of the N-chloramines. Such an intramolecular interaction for the N-chloramines can explain at least in part why these molecules are less potent as antimicrobial agents than are the N,N-cichloramine analogues for which a similar intramolecular interaction is impossible.

Anti-Infective Agents, Local↗
PubMed1977

Improved delivery through biological membranes. 4. Prodrugs of L-dopa.

Various classes of transient derivatives of L-Dopa have been synthesized, systematically protecting one or more of the main sites of metabolism in the molecule: the carboxy function, the amino, and/or the catechol system. The derivatives studied include carboxy esters, phenol esters, amides, peptides, and various combinations of these functions. A number of these derivatives effectively prevent the metabolism of L-Dopa prior to and/or during the absorption process, resulting in a significantly better bioavailability of the drug. In vivo studies using dogs showed up to 2.5-fold increase in L-Dopa blood levels. The metabolism as well as toxicity aspects of the prodrugs is also discussed.

Administration, Oral↗
PubMed1976

N-halo derivatives III: stabilization of nitrogen-chlorine bond in N-chloroamino acid derivatives.

The chlorination of alpha-amino acids and their related derivatives was investigated. A kinetic study of the stability of these N-chlorinated products led to an elucidation of the factors that significantly influence the stability and reactivity of the nitrogen-chlorine bond in these N-chloramines. From the kinetic investigations, a series of low chlorine potential, soft antimicrobial N-chloramines was developed based on derivatives of alpha-aminoisobutyric acid and related compounds.

Amino Acids↗