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At least 19 recordsLinked to original sources
PubMed1986

5,5-Diaryl-2-thiohydantoins and 5,5-diaryl-N3-substituted-2-thiohydantoins as potential hypolipidemic agents.

A series of 5,5-diaryl-2-thiohydantoins and 5,5-diaryl-N3-substituted-2-thiohydantoins related to 5,5-diphenyl-2-thiohydantoin (DPTH) were investigated as potential hypolipidemic agents with the goal of increased potency over DPTH itself. In the 5,5-diaryl class, the best results were obtained by substituting two pyridyl rings for the phenyl rings found in DPTH. The resulting compound, 5,5-bis(2-pyridyl)-2-thiohydantoin, DPYTH (5), had slightly better activity than DPTH in lowering liver cholesterol values. Further modifications to DPYTH (5) are underway and will be the subject of a future report. In the N3 nitrogen-substituted series one compound, 5,5-diphenyl-N3-n-butyl-2-thiohydantoin, DPBTH (7), showed promise during initial screening, but when analyzed in a dose-response study, its activity was considerably less than that of the parent compound DPTH.

Animals↗
PubMed1990

Capillary zone electrophoresis separation and laser-based detection of both fluorescein thiohydantoin and dimethylaminoazobenzene thiohydantoin derivatives of amino acids.

Capillary zone electrophoresis is employed for the separation and analysis of both fluorescein thiohydantoin and dimethylaminoazobenzene thiohydantoin derivatives of amino acids. Detection of minute amounts of these amino acid derivatives is an important milestone in the development of a high sensitivity protein sequencer. Current detection limits for the fluorescein derivative is on the order of 10(-21) moles whereas detection limits for the dimethylaminoazobenzene derivative is on the order of 10(-16) moles.

Amino Acids↗
PubMed2000

The alkylated thiohydantoin method for C-terminal sequence analysis.

The alkylated-thiohydantoin method for C-terminal sequencing makes a significant improvement to the thiohydantoin method first described by Schlack and Kumpf. Prior to cleavage from the protein, the C-terminal thiohydantoin is alkylated, making it a better leaving group than the unmodified thiohydantoin. The C-terminal alkylated-thiohydantoin can be cleaved from the protein under conditions that simultaneously form the next thiohydantoin. Combining cleavage and thiohydantoin formation in one step eliminates the need for activating the C-terminal carboxyl group before every sequencing cycle and prevents detection of C-termini formed by random cleavage of peptide bonds in the protein during the sequencing chemistry. The alkylated-thiohydantoin method includes the presequencing modification of cysteine and lysine and the automated modification of aspartic and glutamic acids, serine and threonine. Modifying the reactive side-chain groups improves the ability to sequence through and detect these amino acids. The alkylated-thiohydantoin method can sequence through and detect 19 of the 20 genetically coded amino acids. Sequencing stops at proline residues.

Alkylation↗
PubMed1988

Structural requirements for hydantoins and 2-thiohydantoins to induce lymphoproliferative popliteal lymph node reactions in the mouse.

The ability of a large number of hydantoins and 2-thiohydantoins to induce primary local lymphoproliferative popliteal lymph node (PLN) reactions has been investigated, as judged by PLN weight enlargement, in an attempt to evaluate the discriminating potential of the PLN reaction to low mol. wt chemicals and to establish structure-activity relationships. Among a series of nineteen hydantoins and related compounds only 5,5-diphenylhydantoin (phenytoin), its major metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin, 5,5-diphenyl-2-thiohydantoin and N-(5-nitro-2-furfurylidene)-1-aminohydantoin (nitro-furantoin) elicited marked PLN reactions in C57BL/6J mice. In DBA/2 mice, PLN responses to the aforementioned compounds were considerably less or virtually absent. A number of hydantoin derivatives and related compounds with one phenyl group and/or other substituents at the 1,3 or 5 position induced only slightly elevated or suppressed PLN responses in C57BL/6J mice. The influence of polar, and lipophilic aliphatic and aromatic substituents at the 5 position were compared among a series of 22 3-methyl-2-thiohydantoin as well as 21 3-phenyl-2-thiohydantoin amino acid derivatives for their ability to elicit primary PLN reactions in C57BL/6J mice. Substitution with only one aromatic group at the 5 position seemed to be necessary to induce PLN enlargements to 2-thiohydantoins already substituted at the 3 position with a methyl group or even more pronounced when substituted with a phenyl group. p-Hydroxylation of 5-benzyl-3-phenyl-2-thiohydantoin significantly diminished the PLN response. In contrast, p-hydroxylation of one of two phenyl groups as in 5-(p-hydroxyphenyl)-5-phenylhydantoin had little effect on lymphoproliferative PLN reactions. The presence of a hydroxyl group in a non-aromatic cyclic substituent as in hexahydro-6-hydroxy-2-methyl-3-thioxo-1H-pyrrolo[1,2-c]imidazol-1- one had no effect on the PLN reaction. A series of aliphatic substituents in the 5 position of 2-thiohydantoins showed that the number of carbon atoms of the substituents as well as the position of side chains in the isomer, rather than the methyl or phenyl group in the 3 position of the 2-thiohydantoin molecule, determined the strength of the PLN enlargement. It is concluded that the PLN weight increase assay appears to be able to discriminate between subtle chemical differences as studied with a large series of hydantoin and 2-thiohydantoin derivatives. The PLN assay may therefore be useful as a preliminary short-term screening method for identification of (classes of) compounds able to induce lymphoproliferative reactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1979

The destruction of serine and threonine thiohydantoins during the sequence determination of peptides by 4-N,N-dimethylaminoazobenzene 4'-isothiocyanate.

1. A mechanism for the destruction of serine and threonine thiohydantoins during protein sequence analysis by the Edman-type degradation is proposed. The mechanism begins with the dehydration of serine and threonine side chains (at the cyclization stage) which occurs mainly in anhydrous acid solution. The dehydrated derivatives finally polymerize by way of the reactive methylene group (enamine) to form polymers with various molecular weights. In aqueous acid solution, the dehydrated thiohydantoins of serine and threonine undergo hydration (according to the Markovnikov rule) and ring fission, which leads to the irreversible breakdown of thiohydantoin ring. The serine derivative shows a much greater tendency to undergo these side-reactions than the threonine derivative. 2. In the presence of oxygen, the alkaline hydrolysis of amino acid thiohydantoins goes through an oxidation-deamination reaction at the C-N bond of the thiohydantoin ring and leads to the formation of thiourea derivative and keto acids. This reaction mechanism accounts for the low recoveries of amino acid obtained from the alkaline hydrolysis of amino acid thiohydantoins.

Amino Acid Sequence↗
PubMed1958

Antithyroid activity of thiohydantoins.

The antithyroid activity of 2-thiohydantoin and some derivatives has been measured in rats, after a single dose and, also, after daily administration for 6 weeks. 2-Thiohydantoin and its 5-alkyl derivatives from 5-methyl to 5-sec-butyl- showed considerable antithyroid activity at a dose of 0.05 m.mole/kg. by mouth, but 5-n-hexyl-2-thiohydantoin had insignificant activity at this dose level. The presence of polar groups in the 5-substituent was associated with reduction or complete loss of activity. By the single-dose technique, 2-thiohydantoin was more potent than its 5-alkyl derivatives. The opposite result was obtained by other methods of assessment after 42 days of treatment. Some of the possible factors involved are discussed especially in relation to the difficulty of comparing results obtained by the different methods of assessment. The acute toxicity of 2-thiohydantoin and of its 5-methyl and 5-ethyl derivatives is reported. No toxic effects were found after daily administration of several 2-thiohydantoins at a dose of 50 mg./kg. for 6 weeks.

Animals↗
PubMed1977

Improved chromatographic identification of coloured amino acid thiohydantoins.

A new N-terminal reagent for peptides and proteins, 4-N,N-dimethylamino-naphthylazobenzene-4'-isothiocyanate, is described which gives purple thiohydantoin derivatives; chromatographic separation of 24 amino acid thiohydantoins is reported. Such standard purple derivatives can be used as markers in the separation of the red 4-N,N-dimethylaminoazobenzene-4'-thiohydantoins. Conversely, standard red thiohydantoins can be used as markers in the separation of unknown purple amino acid thiohydantoins. In two-dimensional thin-layer chromatography, the precision of identifying the unknowns can be greatly improved by running markers with a colour different from the unknowns on the same side of the sheet.

Amino Acids↗
PubMed1992

Formation of proline thiohydantoin with ammonium thiocyanate: progress towards a viable C-terminal amino-acid-sequencing procedure.

Pure amino acid thiohydantoins are required as reference standards for development of C-terminal-sequencing procedures based on thiohydantoin formation of the C-terminal amino acids of peptides and proteins. Proline thiohydantoin was prepared using a straightforward method involving reaction of acetylproline with ammonium thiocyanate. It was characterized by UV spectrophotometry, mass spectrometry and back-hydrolysis to the free amino acid. These data establish unequivocally that the thiocyanate procedure is applicable to proline as well as to the other common amino acids. This work also validates earlier claims that proline thiohydantoin can be prepared by reaction with thiocyanic acid.

Amino Acid Sequence↗
PubMed2005

Enzymatic synthesis of a new inhibitor of alpha-amylases: acarviosinyl-isomaltosyl-spiro-thiohydantoin.

Synthesis of acarviosinyl-isomaltosyl-spiro-thiohydantoin in yields up to 20%, has been achieved by Bacillus stearothermophilus maltogenic amylase (BSMA). BSMA is capable of transferring the acarviosine-glucose residue from an acarbose donor onto glucopyranosylidene-spiro-thiohydantoin. Reactions were followed using HPLC and MALDI-TOF MS. 1H and 13C NMR studies revealed that the enzyme reserved its stereoselectivity. Glycosylation took place mainly at C-6 resulting in alpha-acarviosinyl-(1-->4)-alpha-D-glucopyranosyl-(1-->6)-D-glucopyranosylidene-spiro-thiohydantoin. This compound was found to be a much more efficient salivary amylase inhibitor than glucopyranosylidene-spiro-thiohydantoin with kinetic constants of K(EI)=0.19 microM and K(ESI)=0.24 microM.

Enzyme Inhibitors↗
PubMed1997

Solution-Phase Synthesis of a Combinatorial Thiohydantoin Library(1).

An efficient one-pot three-component synthesis of thiohydantoins was developed. In the first step, amino acid esters were alkylated by imine formation with aldehydes and reduction by sodium triacetoxyborohydride. In the second step, an isothiocyanate was added together with a molar equivalent of triethylamine, leading to the thiohydantoin product in high yield and purity after an extractive aqueous workup. This procedure was used to generate a combinatorial library of over 600 discrete thiohydantoins on a 0.1 mmol scale. Sampling of 10% of this library showed the thiohydantoin to be the major product in all cases, with purities of 52-98% by HPLC analysis. The cyclization conditions can also be adapted to the synthesis of hydantoins.

Journal Article↗
PubMed1997

A method for preparation of amino acid thiohydantoins from free amino acids activated by acetyl chloride for development of protein C-terminal sequencing.

A novel and efficient method to prepare amino acid thiohydantoins, which are required as reference standards for development of C-terminal protein sequencing, is reported. Amino acid thiohydantoins were prepared using a straightforward method involving reaction of 20 free amino acids with acetyl chloride as activating reagent and trimethylsilyl isothiocyanate (TMS-ITC) as derivatizing reagent. The products were characterized by HPLC, uv spectra, amino acid analysis, MS, and NMR. Different reaction conditions were investigated and the chemical mechanism of the formation of amino acid thiohydantoins was illustrated.

Acetates↗
PubMed2001

Glycosylation of 2-thiohydantoin derivatives. Synthesis of some novel S-alkylated and S-glucosylated hydantoins.

3-Aryl-5-((Z)-arylidene)-3-aryl-2-(2-methylthioethyl)-2-thiohydantoins 3a-f and 3-aryl-5-((Z)-arylidene)-2-(2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyl)-2-thiohydantoins 7a-n were prepared from the reaction of 3-aryl-5-((Z)-arylidene)-2-thiohydantoins 2a-n with methylthioethyl chloride or 2',3',4',6'-tetra-O-acetyl-alpha-D-glucopyranosyl bromide via three different routes. The compounds did not display any antiviral and antitumoral activity.

Antineoplastic Agents↗
PubMed2001

Synthesis of 2-thiohydantoins and their S-glucosylated derivatives as potential antiviral and antitumor agents.

A series of 3-alkyl-5-((Z))-arylidene-2-thiohydantoins 4a-1 were synthesized from the direct condensation of the aromatic aldehydes with 3-alkyl-2-thiohydantoins 3a-c, which in turn were prepared from the reaction of glycine (1) and alkyl isothiocyanates 2a-c. The alkylation of 4a-1 with methylthioethyl chloride gave 5-((Z))-arylidene-3-alkyl-S-(2-methylthioethyl)-2-thiohydantoins 5a-e. S-Glucosylation took place on the reaction of 4a-1 with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide under anhydrous alkaline conditions. These structures have been confirmed from a model study of the coupling of 4a with methylthioethyl chloride and alpha-D-glucose pentaacetate, respectively under Lewis acid conditions.

Alkylation↗
PubMed1977

Identification of 3-methyl-2-thiohydantoin, a metabolite of carbimazole, in man.

1. Classical and high-pressure liquid chromatographic separations were devised for the separation and isolation of the metabolite 3-methyl-2-thiohydantoin from the urine of patients receiving carbimazole orally. 2. 3-methyl-2-thiohydantoin was identified by comparing its absorption and mass spectral properties with authentic material. 3. 3-methyl-2-thiohydantoin was also detected in the plasma of patients receiving methimazole intravenously.

Carbimazole↗