Positron annihilation lifetime studies of changes in free volume on some biorelevant nitrogen heterocyclic compounds and their S-glycosylation.

A series of N-heterocyclic compounds was investigated by positron annihilation lifetime spectroscopy as well as Doppler broadening of annihilation radiation (DBAR) at room temperature. The results showed that the formation probability and life time of ortho-positronium in this series are structure and electron-donation character dependent, and can give more information about the structure. The DBAR provides direct information about the change of core and valance electrons as well as the number of defect types present in these compounds.

Subarachnoid hemorrhage of unknown origin and the basilar artery configuration.

It is unclear whether the configuration of the basilar artery (BA) in patients with subarachnoid hemorrhage (SAH) of unknown origin is comparable to that in normal subjects or whether there are differences which may help to identify the origin. We studied the BA configuration in 57 patients with SAH of unknown origin (10%), who were identified in a prospectively collected series of 549 SAH patients consecutively admitted to our service over a 9-year period. There were 30 patients (53%) with non-perimesencephalic SAH and 27 with perimesencephalic SAH (47%). According to a standardized algorithm we determined, on straight anteroposterior digital subtraction angiography (DSA), the width of the proximal BA segment at the origin of the anterior inferior cerebellar artery and the width of the most distal BA segment between the superior cerebellar arteries and the posterior cerebral arteries. Based on these measurements we calculated the distal-proximal BA ratios and compared them to the ratios obtained in a control group of 31 patients who had DSA for reasons other than aneurysmal SAH. The mean ratio in patients with non-perimesencephalic SAH of unknown origin was 1.150 (range: 1.080-1.230). In patients with perimesencephalic SAH of unknown origin it was 1.156 (range: 1.120-1.250). In the control group the mean ratio was 1.163 (range: 1.125-1.200). There are no variations in the configurations of the BA which could possibly explain the cause of this type of SAH or clarify the origin of hemorrhage.

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.

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.

Synthesis of arylidenehydrazono- and glycopyranosylhydrazino-sulfonylbenzylidene-2,4-imidazolidinediones as potential antiviral and antitumoral agents.

A series of 5-[(Z)-(4-(2-(E)-arylidene)hydrazonosulfonylbenzylidene)]-2, 4-imidazolidinediones 6a-h and 5-[(Z)-(4-(2-beta-D-glycopyranosyl) hydrazinosulfonylbenzylidene)]-2,4-imidazolidinediones 10a-j were synthesized via two different routes. The compounds did not display any antiviral and antitumoral activity.

Sugarhydrazones of 2-hydrazinoquinolines and their antimicrobial activity.

Sugar hydrazones from 2-hydrazinoquinoline, 2-hydrazino-6-methyllepidine, 6-chloro-2-hydrazino lepidine, 7-chloro-2-hydrazinolepidine, and 7-chloro-2-hydrazino-3-nitroquinoline were prepared. Their acetylation, benzoylation, periodate oxidation, oxidation with lead tetraacetate and bromination have been investigated. The antimicrobial activities of the hydrazones were evaluated. Some compounds showed moderate activity.

Synthesis of certain 5-substituted 2-thiohydantoin derivatives as potential cytotoxic and antiviral agents.

A convenient route is reported for the synthesis of certain series of 2-thiohydantoins carrying various heterocyclic substituents such as 5-bromothienylidene 3a,b, 5-(2-carboxyphenylthio)-2-thienylidene 4a,b and 4H-thieno[2,3-b][1]benzothiopyran-4-one 5a,b. Glycosylation of these thiohydantoins afforded the S-glycosyl derivatives 10a-d. The synthesized compounds were tested for their activity against HIV-1 virus and as antitumor agents.

5-substituted-2-thiohydantoin analogs as a novel class of antitumor agents.

Certain series of 2-thiohydantoin derivatives, carrying various substituents at position 5 such as 5-bromo-2-thienylmethylene, 5-(2-carboxyphenylthio)-2-thienylmethylene and 2-methylene-4H-thieno[2,3-b][1]benzothiopyran-4-one, were evaluated for their antitumor activity. Compound 5-(5-bromo-2-thienylmethylene)-3-morpholinomethyl-2-(2,3,4,6 -tetra-O-acetyl -beta-D-glucopyranosylthio)hydantoin proved to possess a broad spectrum antitumor activity against a wide range of different human cell lines of nine tumor subpanels causing both cytostatic and cytotoxic effects, resulting in full panel median growth inhibition (GI50) and total growth inhibition (TGI), with a median lethal concentration (LC50) at 15.1, 41.7 and 83.2 microM, respectively. On the other hand, compound 5-(5-bromo-2-thienylmethylene)-2-thiohydantoin and compound 5-(5-bromo-2-thienylmethylene)-3-phenyl-2- (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-thio)hydantoin showed potential selectivity against leukemia cell lines. Further derivatization of these compounds, deduced from the obtained tentative structure-activity relationships, may lead to more potent agents.

Synthesis and antiviral evaluation of hydantoin analogues of AZT.

3'-Azidonucleosides 4 have been synthesized by condensation of silylated (Z)-5-ethylidenehydantoin and (Z)-5-benzylidenehydantoin with methyl 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-pento furanoside (3). The nucleosides 4 were deblocked on treatment with tetrabutylammonium fluoride. The ethylidene group isomerized from Z to E configuration during the nucleoside synthesis. The new nucleosides did not show any appreciable activities against HIV-1 or HSV-1.

S-glucosylated hydantoins as new antiviral agents.

S-Glycosylation took place on reaction of 5-alkylidene- and 5-arylidene-3-aryl-2-thiohydantoins with glycosyl halides under alkaline conditions. Bisglucosylation also took place when N-3 unsubstituted hydantoins were reacted. The bisglucosylated hydantoins produced N-3 glucosylated hydantoins on treatment with ammonia in methanol. In antiviral studies the most active compounds against both HSV-1 and HSV-2 were 5-(2-thienylmethylene)-3-phenyl-2-(2,3,4,6- tetra-O-acetyl-beta-D-glucopyranosyl)-2-thiohydantoin and 5-(2-thienylmethylene)-3-(4-chlorophenyl)-2-(2,3,4,6-tetra-O-acety l-beta-D- glucopyranosyl)-2-thiohydantoin.

The mechanism of methyl mercury toxicity in isolated rat hepatocytes.

Mercury is the major component of dental amalgam restorative material, which typically has 50% pure elemental mercury. It is also used in some skin creams, and in the manufacturing of plastic, drugs and fungicides. The present study was designed to investigate the toxicity of methyl mercury (MeHg+) on isolated rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and were incubated with different concentrations of MeHg+ (0.1-100 ppm) for 2 h. Through the incubation period the viability was determined by Trypan blue exclusion. Reduced glutathione (GSH) content and its enzymes, glutathione peroxidase (GSH-PX) and glutathione reductase (GSH-RX) were measured. Leakage of enzymes such as aspartate transaminase (AST), and alanine transaminase (ALT) were determined. The cell viability was reduced significantly after 1 h incubation when 0.1 and 1 ppm MeHg+ were applied. The decrease in the cell viability was dose- and time-dependent. A depletion of GSH content was observed with 100 ppm MeHg+ after 30 min of incubation. A significant decrease in GSH-RX was observed with 100 ppm during 15 and 30 min of incubation, while 10 ppm of MeHg+ significantly increased ALT leakage after 60 min. However, there was a significant increase in AST leakage with 100 ppm only. The present investigation indicates that the toxic effect of MeHg+ is most likely cytosolic enzyme related.

Lipase productivity of a lipolytic strain of Thermoactinomyces vulgaris.

An attempt was made to evaluate the lipase productivity by Thermoactinomyces vulgaris with various nutritional and environmental factors. Results suggest optimum conditions for production, viz. age of inoculum 18 hours, 55 degrees C, pH 6.8, 0.2% yeast extract, specific substrates, and shaken cultures incubated for 24--36 hours. Lipases are induced by corn oil in presence of yeast extract or of certain substitutes; starch could replace these at 55 degrees C. A suggestion is given of a regulatory system of lipase synthesis, involving the supply of starch to initiate growth, allowing induction of lipase by the inductive substrate.

Identity and lipase activity of an isolate of Thermoactinomyces vulgaris.

An actinomycete with thermophilic nature and strong lipolytic activity was isolated by enrichment from an Egyptian soil. It proved to be Thermoactinomyces vulgaris. Variabilities justifying Adansonian systematics were reported and discussed. The potential relation of an occasional drop in successfully resumed activity to an auto-inhibition phenomenon has been notified. Optimum conditions for the activity of the extracellular lipase(s), including stability, suggest the practical importance of the enzyme(s) in the growth filtrates.