Showing papers in "Archives of Pharmacal Research in 1987"

Refinement of the structure of naproxen, (+)-6-methoxy-α-methyl-2-naphthaleneacetic acid

Abstract: The molecular structure of naproxen determined by X-ray diffraction technique was refined to the final R-value being 0.042. The compound was recrystallized from ethanol solution in monoclinic crystal system, space group P21, with Z=2,a=13.375(5) A,b=5.793(2) A,c=7.914(3) A, β=93.91(3) A andd obs=1.26,d calc=1.25g/cm3. The structure was solved by direct method and refined by block diagonal least squares procedure for 747 reflections(F≧6 σ (F)). The molecules are connected by two intermolecular OH-O type hydrogen bonds.

Sedative activity and its active components of Zizyphi fructus

Abstract: Sedative activity of Zizyphi fructus was evaluated by potentiation of hexobarbital-induced hypnosis test and its active principles have been characterized as nornuciferine and lysicamine. A new cyclopeptide alkaloid, daechucyclopeptide-1 was isolated together with zizyphusine.

Alkaloids are the sedative principles of the seeds of Zizyphus vulgaris var. spinosus

Abstract: Sedative principles of the seeds ofZizyphus vulgaris varspinosus have been characterized as sanjoinine-A (frangufoline), nuciferine and their congeners Also, heattreatment of sanjoinine-A produced a more active artifact, sanjoinine-Ahl, which provides a scientific basis for heat-processing (roasting) of this Oriental medicine

Antithrombotic activities of saponins fromIlex pubescens

Abstract: Methanol extract ofIlex pubescens roots prolonged bleeding time threefold, and inhibitied the generation of malondialdehyde released during platelet aggregation induced by thrombin. Through several purification procedures, its saponin, named ilexoside, was proved to be responsible for the antithrombotic activities of the plant. Ilexosides A,-D and-J, and 24-carboxypomolic acid showed strong inhibitory activities on platelet aggregation induced by thrombin.

Triterpenoid glycosides from rosa rugosa

Abstract: From the underground parts ofRosa rugosa(Rosaceae), 28-O-glucosides of euscaphic acid, tormentic acid and arjunic acid were isolated and characterized by spectral data.

Soyasapogenols B and E fromMelilotus officinalis

Abstract: From the aerial parts ofMelilotus officinalis (Leguminosae) soyasapogenols B, mp 259–260°, and E, mp 246–247°, were isolated along with coumarin and kaempferol. This is the first report of the isolation of soyasapogenols from the genus Melilotus.

New triterpenoid saponins fromIlex pubescens

Abstract: New triterpenoid saponins, ilexosides A,-D,-E,-H,-J,-K and-O, have been isolated from the root ofIlex pubescens. Chemical and spectroscopic studies have established their structures as shown in formulae1,2,8,11,3,4 and5.

Stability and drug release properties of liposomes containing cytarabine as a drug carrier

Abstract: Liposomes were studied as a drug delivery system. Multilamellar vesicles, small unilamellar vesicles and large unilamellar vesicles containing cytarabine were prepared using egg yolk lecithin and cholesterol. Large unilamellar vesicles showed the highest encapsulation efficiency of all and their encapsulation efficiency increased as the buffer volume decreased. Cholesterol increased the stability of liposomal drug products as drug carriers and reduced the permeability of drug across the liposomal membrane. The release rate of cytarabine increased with incubation temperature and decreased with cholesterol incorporation in liposomal membrane. The release mechanism of cytarabine from large unilamellar vesicles in vitro was chiefly due to simple diffusion across the liposomal membrane rather than liposomal rupture.

Studies on protoplast formation and regeneration ofGanoderma lucidum

Abstract: To obtain a new strain ofGanoderma lucidum by protoplast fusion technique, its protoplast formation and regeneration were studied. Several factors affecting the protoplast formation and regeneration were investigated to find their optimum conditions. The mycelium was grown for four days on the cellophane membrane placed onG. lucidum complete medium (GCM). When various commercial lytic enzymes were examined for protoplast isolation, the combination of Novozym 234 and β-glucuronidase was found to be effective. An osmotic stabilizer, 0.6 M sucrose in 20 mM phosphate buffer pH 5.8, gave the highest yield of protoplasts. Three-hour incubation in shaking incubator was most suitable for releasing protoplasts. To increase the protoplast yield, pretreatment with 2-mercaptoethanol was carried out. The regeneration frequency in GCM containing 0.6 M MgSO4·7H2O was shown to be 0.66%.

Studies on the monoamine oxidase inhibitors of medicinal plants I. Isolation of MAO-B inhibitors fromChrysanthemum indicum

Abstract: Fourteen kinds of medicinal plants were screened for determining inhibitory activities on monoamine oxidase B. The extracts ofArtemisia Messer-Schmidtiana (herba),Chrysanthemum indicum (flos),Ericibe obtusifolia (radix et rhizoma) andSophora japonica (flos) strongly inhibited the enzyme. Among them, Chrysanthemi flos was chosen for elucidating its active principles, and some flavonoids were isolated and identified as acacetin (I), 5,7-dihydroxy chromone (II), diosmetin (III), apigenin (IV), eriodictyol (V) and luteolin (VI). IC50-dihydroxy chromone (II), diosmetin (III), apigenin (IV), eriodictyol (V) and luteolin (VI). IC50 were determined as following: I, 2.46; II, 0.19; III. 2.11mM, and the others showed weak inhibition.

Chemical studies on the ether-soluble alkaloidal fraction ofPanax ginseng. Isolation of 1-carbobutoxy-β-carboline and 1-carbomethoxy-β-carboline

Abstract: Two alkaloids were isolated from an ether-soluble alkaloidal fraction ofPanax ginseng. They were identified as 1-carbobutoxy-β-carboline and 1-carbomethoxy-β-carboline.

Further study on the constituents ofRhododendron brachycarpum

Abstract: From the leaves ofRhododendron brachycarpum, rhododendrin, grayanotoxin I and guaijaverin were isolated and characterized by spectral data.

Spinacine fromPanax ginseng

Abstract: An alkaloid was isolated from water-soluble fraction ofPanax ginseng roots. It was characterized by spectroscopic data and synthesis as 4,5,6,7-tetrahydroimidazo(4,5-c) pyridine-6-carboxylic acid or spinacine, which was first isolated from the plant kingdom.

Effect ofPanax ginseng on the development of morphine induced tolerance and dependence (VI). On the oral administration of ginseng ether fraction and saponins

Abstract: The present study was undertaken to determine the inhibitory effects of orally adminstered ginseng saponins(GS), protopanaxadiol saponins(PD), protopanaxatriol saponins(PT) and ginseng ether fraction(GE) on the development of morphine induced tolerance and physical dependence in mice and also to determine the hepatic glutathione contents. GS, PD and PT inhibited significantly the development of morphine induced tolerance and physical dependence, but GE was effective only on the inhibition of the development of morphine induced physical dependence. GS, PD, PT and GE also inhibited the hepatic glutathione level decrease induced by morphine multiple injections.

Determination of blood concentration of higenamine by high pressure liquid chromatography

Abstract: A procedure utilizing high pressure liquid chromatography coupled with UV detection is described for the determination of blood concentration of higenamine. Deproteinized serum was pretreated with C18 (Sep-pak C18 cartridge) and the 70% EtOH eluent was applied onto a reversed-phase column (μ Bondapak C18) with a 15% acetonitrile in 0.05 N NaH2 PO4-trichloroacetic acid mixed buffer (pH 2.8) as a mobile phase. With the UV detection at 232 nm, the retention times of higenamine and 1,2,3,4-tetrahydropapaveroline, an internal standard, were 5.2 min and 3.9 min respectively. The blood concentration of higenamine was measured at regular intervals afteri.v. injection of higenamine to rabbit. A drastic decrease in higenamine concentration to 30% of the maximum value obtained immediately after the injection, was observed during the first 1–2 min period and thereafter the rate of decrease was slowed down. The analytical result seemed to coincide with the pharmacological effect of higenamine exerting the maximum chronotropic and hypotensive effect at the completion of the injections which were progressively recovered.

Reactions with heterocyclic amidines (V). Synthesis of some new imidazo[1,2-b] pyrazole, pyrazolo [5,1-c]-1,2,4-triazine and pyrazolo [5,1-c]-1,2,4-triazole derivatives

Abstract: Several new imidazo [1,2-b] pyrazole, pyrazolo [5,1-c]-1,2,4-triazine and pyrazolo [5,1-c] triazole derivatives were prepared from the reaction of 3-antipyrinyl-5-aminopyrazole or its diazonium salt with α-chloroacetyl derivatives.

Absolute configuration of sanjoinine-A (frangufoline) and its heat induced artifact; sanjoinine-Ahl

Abstract: Frangufoline (sanjoinine-A)1) (1) was transformed into its epimer, sanjoinine-Ah1(2), on heat treatment. Absolute configuration of (1) and (2) was determined.

Quantitative analysis by derivative spectrophotometry (II)

Abstract: One of the problems of derivative spectrophotometry, the decrease of signal-to-noise ratio by derivative operations, was solved by three concepts of digital filtering, ensemble averaging, least squares polynomial smoothing and Fourier smoothing. The authors made several computer programs written in APPLE SOFT BASIC language for the actual applications of the concepts of these digital filters on UV spectrophotometer system. As a result, ensemble averaging could not be used as a routine operation for the spectrophotometer used. The maximum S/N ratio enhancement factors achieved by least squares polynomial smoothing were 6.17 and 7.47 for the spectra of Gaussian and Lorentzian distribution models, and by Fourier smoothing, 16.42 and 11.78 for the spectra of two models, respectively.

Triterpenoids ofIlex pubescens

Abstract: Four triterpenoids were isolated from the roots ofIlex pubescens: two new triterpenoids named pubescenolic acid (I) and pubescenic acid (II), and two known triterpenoids ilexolic acid (III) and oleanolic acid (IV). Chemical and spectroscopic studies have establishedI andII as 20-epipomolic acid and 24-carboxypomolic acid, repectively.

Effect of salts on the entrapment of calf thymus DNA into liposomes

Abstract: To correlate the conformational changes of DNA (Calf Thymus) with entrapment of DNA into lipsomes, the effect of ions(Na+, Mg++) on the entrapment of calf thymus DNA into liposomes was investigated. The effect of divalent ion(Mg++) on the structural changes of DNA indicated by decrease of observed ellipticity at 274 nm and nonspecific binding of DNA to lipid bilayers was greater than monovalent ion(Na+). But the efficiency of DNA encapsulated was not altered. These results show that entrapment of DNA into liposomes is not due to nonspecific binding and structural changes because of electrostatic forces but to mechanical capture of DNA by the internal aqueous space of liposomes although divalent ion contributes large structural changes and more nonspecific association of DNA with liposomes due to strong charges.

Intravascular tumour targeting of aclarubicin-loaded gelatin microspheres. Preparation, biocompatibility and biodegradability

Abstract: This study is to evaluate the potential use of aclarubicin-loaded gelatin microspheres as an intravascular biodegradable drug delivery system for the regional cancer therapy. The diameter of the microspheres prepared by water in oil emulsion polymerization could be controlled by adjusting the stirring rate in the range of 10–50 μm: D(in μm)=−73.8 log(rpm)+262.7. The addition of proteolytic enzyme increased the in vitro aclarubicin release, but it did not change the amount of the initial burst release which reached about 45%. Microspheres injected intravenously into the mouse tail vein embolized only to the lung when observed by fluorescence microscopy. From histological examination following injection of gelatin microspheres into mouse femoral muscle, mild inflammation was observed from the appearance of neutrophils after 2 days and rapid repair process was confirmed thereafter. Biodegradation process of gelatin microspheres lodged on the pulmonary capillary bed was followed up by microscopic observation; degradation was taking place by about 36 hrs, followed by severe damage on the spherical shape and microspheres was no longer found 10 days after injection.

Studies on the Korean indigenous plants. Isolation of 1-eicosanoyl cafferate fromEchinosophora koreensis

Abstract: 1-Eicosanoyl cafferate, mp 109–110°, was isolated from the underground parts ofEchinosophora koreensis together with hexacosanol, mp 75–6°. 1-Eicosanoyl cafferate was isolated for the first time from plant source.

Effect of scoparone on the hepatic microsomal UDP glucuronyltransferase activity in mice

Abstract: The effect of scoparone on UDPglucuronyltransferase in mouse hepatic microsomes was studied. After treatment with scoparone, hepatic microsomal UDPglucuronyltransferase activity was increased with dose-dependent manner as compared to control. The Vmax value (control=23.2 n moles/mg protein/min, scoparone=31.2 n moles/ mg protein/min) without affecting the Km value (414 μM) for p-nitrophenol was increased by the scoparone treatment, and the pattern of kinetic studies for UDP-glucuronic acid was also similar to those of p-nitrophenol. Whereas, the hepatic microsomal UDPglucoronyltransferase was not changed by the addition of scoparone in vitro. The results obtained suggest that the characteristics of increase in the enzyme activity may include induction of enzyme proteins.

In vivo immunotoxicities of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) in male mice

Abstract: The effects of butylated hydroxyanisole and butylated hydroxytoluene on the immune status in normal male mice were evaluated. They exhibited the significant decrease in the circulating leukocyte counts. Relative spleen and thymus weights were slightly decreased, but not statistically significant. There were, however, significant liver hypertrophies in their exposed mice. Splenic IgM PFCs per one million cells in 1/20 LD50 BHA and BHT exposed mice were significantly reduced. IgM PFCs per spleen were similar to those of control, except in 1/20 LD50 BHA exposed mice, where they were significantly suppressed. The precise nature of the inhibition is not clear. Direct cytotoxicity is not responsible for the depressed antibody response, even following relatively high doses of them, because the changes in spleen cellularity are not significant. Both substances, however, did not show any effects on the arthus reaction and delayed hypersensitivity reaction induced by heat-aggregated bovine serum albumin, andin vivo phagocytosis of colloidal carbon. In the light of the present results,in vivo antibody response as well asin vitro, may be sensitive to BHA and BHT. Further elucidation of the precise nature of antibody suppression in their exposed mice, is warranted.

Antitumor constituents ofPolyporus giganteus

Abstract: To investigate antitumor constituents of higher fungi, the carpophores ofPolyporus giganteus Pers ex Fr (81 g, dry weight) which were collected in Indiana, USA were examined for antitumor activity Two protein-bound polysaccharide fractions (I and II) were prepared from the hot water extract and one fraction (III) from the 01 N NaOH extract of the carpophores The antitumor effect of each fraction was tested against sarcoma 180 implanted subcutaneously in female ICR mice Of three fractions, Fraction II showed 852% inhibition ratio at the dose of 20 mg/kg/day for 10 days and was named gigantan Gigantan was found to contain 59% polysaccharide and 27% protein Its polysaccharide moiety was a heteroglycan that consisted of mainly glucose (893%), galactose (77%), manose (20%) and fructose (10%)

Effect of carbon tetrachloride intoxication on the type conversion of xanthine dehydrogenase into xanthine oxidase in rats

Abstract: The conversion of xanthine dehydrogenase(type D) into xanthine oxidase(type O) was significantly increased in serum and liver of all CCl4 treated rats on the necrosis and early cirrhosis stage of liver tissue. In the pretreatment of prednisolone, the ratio of type O per type O+D showed the decreasing tendency in serum but the significant decrease in liver.In vitro, the conversion of liver xanthine oxidase from type D into type O was markedly increased by following preincubation with lysosomal fraction. The type conversion of xanthine oxidase may be caused by proteolytic enzymes in lysosome.

Synthesis of imidazole derivatives containing biologically active units

Abstract: Reaction of oxazolin-5-ones1 withp-amino-diphenylamine was resulted in the formation of the corresponding imidazolin-5-ones2 which on treatment with sulphur afforded phenothiazines3. Acridine derivatives5 were obtained from acetylaminodiphenylamines derivatives6 on heating with ZnCl2 at 200°C.3 reacted with chloroacetyl chloride to give7 which reacted in turn with different amines to give8. Antibacterial activity of the obtained products was studied.

Development of physiological pharmacokinetic model

Abstract: The development of physiologically based pharmacokinetic model for drug distribution and excretion is described. The physiological modeling procedure is useful in animal and clinical applications to obtain fundamental knowledge of the transport and metabolism of a substancein vivo. In this paper a review of physiologically based pharmacokinetics is presented in the hope of understanding and increasing the use of this modelling technique. The method of model development and the composition of equations based on the different models are explained. For the better understanding a physiological pharmacokinetic model of tenoxicam disposition in the rat is presented as an example of flow limited model.

1-methyl substituent and stereochemical effects of 2-phenylcyclopropylamines on the inhibition of rat brain mitochondrial monoamine oxidase A and B

Abstract: (E)-2-Phenylcyclopropylamine ((E)-TCP), (Z)-2-phenylcyclopropylamine ((Z)-TCP), (E)-1-methyl-2-phenylcyclopropylamine ((E)-MTCP), and (Z)-1-methyl-2-phenylcyclopropylamine ((Z)-MTCP) were synthesized and used to determine to what extent 1-methyl substitution and stereochemistry of 2-phenylcyclopropylamines affect inhibition of monoamine oxidase (MAO). Inhibition of rat brain mitochondrial MAO-A and B by the compounds were measured using serotonin and benzylamine as the substrate, respectively and IC50 values obtained with 95% confidence limits by the method of computation. For the inhibition of MAO-A, (E)-MTCP (IC50=6.2×10−8M) was found to be 37 times more potent than (Z)-MTCP (IC50=2.3×10−6 M), whereas the activity of (E)-TCP (IC50=2.9×10−7 M) was slightly less than that of (Z)-TCP (IC50=2.3×10−7 M). Similarly, for the inhibition of MAO-B, (E)-MTCP (IC50=6.3×10−8 M) was 7 times more potent than (Z)-MTCP (IC50=4.7×10−7 M) and (E)-TCP (IC50=7.8×10−8 M), 0.6 times as potent as (Z)-TCP (IC50=4.4×10−8 M). The results suggested that while without 1-methyl group, potency of a (Z)-isomer was comparable to that of (E)-isomer, the methyl group in its (Z)-position was very unfavorable to the inhibition of MAO and that in its (E)-position, the methyl group contributed positively to the potency as found by the fact that (E)-MTCP was 1–5 times more potent than (E)-TCP. In view of the selective inhibition of MAO-A or B, all compounds elicited 4–10 times higher preference for the inhibition of MAO-B over MAO-A and 1-methyl substitution as well as the stereochemical factors did not significantly influence the selectivity.

Agonist-induced desensitization of muscarinic acetylcholine receptor in rat brain

Abstract: Intact brain cell aggregates were dissociated from adult rat brains without cerebellum using a sieving technique. This preparation was used to elucidate the binding characteristics of agonist to muscarinic acetylcholine receptors (mAchR) in brain. Incubation of cells with carbamylcholine (carbachol) was shown agonist-induced receptor down-regulation depending on the concentration of agonist, not depending on the incubation time. This effect of carbachol was due to a reduction in the maximal binding capacity (B max ) to the mAchR without decreasing the affinity of the remaining receptors in incubation at 37 °C but was not apparent in incubation at 15 °C. In addition, it was abolished when the receptors were blocked by atropine. The decline in (3H)N-methylscopolamine((3H)NMS) binding induced by agonist was reflected as a significant reduction in the receptor density with no change in receptor affinity, suggesting that ‘tru’ receptor down-regulation takes place. Moreover, when the receptors were labeled with the lipophilic antagonist (3)NMS, the magnitude of the observed receptor down-regulation was significantly lower in case of the former than the latter. This suggests that exposure of intact brain cells to muscarinic agonists might induce a slight degree of accumulation of receptors in intracellular sites before the receptors are actually degraded.