Zeitschriften und Ausgaben

Volumen 72 (2022): Heft 4 (December 2022)

Volumen 72 (2022): Heft 3 (September 2022)

Volumen 72 (2022): Heft 2 (June 2022)

Volumen 72 (2022): Heft 1 (March 2022)

Volumen 71 (2021): Heft 4 (December 2021)

Volumen 71 (2021): Heft 3 (September 2021)

Volumen 71 (2021): Heft 2 (June 2021)

Volumen 71 (2021): Heft 1 (March 2021)

Volumen 70 (2020): Heft 4 (December 2020)

Volumen 70 (2020): Heft 3 (September 2020)

Volumen 70 (2020): Heft 2 (June 2020)

Volumen 70 (2020): Heft 1 (March 2020)

Volumen 69 (2019): Heft 4 (December 2019)

Volumen 69 (2019): Heft 3 (September 2019)

Volumen 69 (2019): Heft 2 (June 2019)

Volumen 69 (2019): Heft 1 (March 2019)

Volumen 68 (2018): Heft 4 (December 2018)

Volumen 68 (2018): Heft 3 (September 2018)

Volumen 68 (2018): Heft 2 (June 2018)

Volumen 68 (2018): Heft 1 (March 2018)

Volumen 67 (2017): Heft 4 (December 2017)

Volumen 67 (2017): Heft 3 (September 2017)

Volumen 67 (2017): Heft 2 (June 2017)

Volumen 67 (2017): Heft 1 (March 2017)

Volumen 66 (2016): Heft 4 (December 2016)

Volumen 66 (2016): Heft 3 (September 2016)

Volumen 66 (2016): Heft 2 (June 2016)

Volumen 66 (2016): Heft 1 (March 2016)

Volumen 65 (2015): Heft 4 (December 2015)

Volumen 65 (2015): Heft 3 (September 2015)

Volumen 65 (2015): Heft 2 (June 2015)

Volumen 65 (2015): Heft 1 (March 2015)

Volumen 64 (2014): Heft 4 (December 2014)

Volumen 64 (2014): Heft 3 (September 2014)

Volumen 64 (2014): Heft 2 (June 2014)

Volumen 64 (2014): Heft 1 (March 2014)

Volumen 63 (2013): Heft 4 (December 2013)

Volumen 63 (2013): Heft 3 (September 2013)

Volumen 63 (2013): Heft 2 (June 2013)

Volumen 63 (2013): Heft 1 (March 2013)

Volumen 62 (2012): Heft 4 (December 2012)

Volumen 62 (2012): Heft 3 (September 2012)

Volumen 62 (2012): Heft 2 (June 2012)

Volumen 62 (2012): Heft 1 (March 2012)

Volumen 61 (2011): Heft 4 (December 2011)

Volumen 61 (2011): Heft 3 (September 2011)

Volumen 61 (2011): Heft 2 (June 2011)

Volumen 61 (2011): Heft 1 (March 2011)

Volumen 60 (2010): Heft 4 (December 2010)

Volumen 60 (2010): Heft 3 (September 2010)

Volumen 60 (2010): Heft 2 (June 2010)

Volumen 60 (2010): Heft 1 (March 2010)

Volumen 59 (2009): Heft 4 (December 2009)

Volumen 59 (2009): Heft 3 (September 2009)

Volumen 59 (2009): Heft 2 (June 2009)

Volumen 59 (2009): Heft 1 (March 2009)

Volumen 58 (2008): Heft 4 (December 2008)

Volumen 58 (2008): Heft 3 (September 2008)

Volumen 58 (2008): Heft 2 (June 2008)

Volumen 58 (2008): Heft 1 (March 2008)

Volumen 57 (2007): Heft 4 (December 2007)

Volumen 57 (2007): Heft 3 (September 2007)

Volumen 57 (2007): Heft 2 (June 2007)

Volumen 57 (2007): Heft 1 (March 2007)

Zeitschriftendaten
Format
Zeitschrift
eISSN
1846-9558
Erstveröffentlichung
28 Feb 2007
Erscheinungsweise
4 Hefte pro Jahr
Sprachen
Englisch

Suche

Volumen 66 (2016): Heft 3 (September 2016)

Zeitschriftendaten
Format
Zeitschrift
eISSN
1846-9558
Erstveröffentlichung
28 Feb 2007
Erscheinungsweise
4 Hefte pro Jahr
Sprachen
Englisch

Suche

10 Artikel
Uneingeschränkter Zugang

Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 303 - 330

Zusammenfassung

Abstract

Nanoindentation allows quantitative determination of a material’s response to stress such as elastic and plastic deformation or fracture tendency. Key instruments that have enabled great advances in nanomechanical studies are the instrumented nanoindenter and atomic force microscopy. The versatility of these instruments lies in their capability to measure local mechanical response, in very small volumes and depths, while monitoring time, displacement and force with high accuracy and precision.

This review highlights the application of nanoindentation for mechanical characterization of pharmaceutical materials in the preformulation phase (primary investigation of crystalline active ingredients and excipients). With nanoindentation, mechanical response can be assessed with respect to crystal structure. The technique is valuable for mechanical screening of a material at an early development phase in order to predict and better control the processes in which a material is exposed to stress such as milling and compression.

Schlüsselwörter

  • instrumented nanoindentation
  • mechanical properties
  • Young’s modulus
  • indentation hardness
  • fracture toughness
  • crystalline active ingredients and excipients
Uneingeschränkter Zugang

Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 331 - 351

Zusammenfassung

Abstract

6ʹ-(4-Chlorophenyl)-spiro[cyclohexane-1,2ʹ-thieno[3,2-d][1,3] oxazin]-4ʹ(1ʹH)-one (1) was synthesized and used as a starting material for the synthesis of a novel series of spiro compounds having biologically active sulfonamide 2a-e and 3ʹ-(4-acetylphenyl)-6ʹ- (4-chlorophenyl)-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d] pyrimidine-4ʹ(3ʹH)-one (3). Compound 2a was used as a key intermediate for the synthesis of sulfonyl carbothioamide derivatives 4a-c. Also, compound 3 was used as an intermediate for the synthesis of 3ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidin]-3ʹ-yl] phenyl}-2-imino-4-(substituted phenyl and/or thienyl)-1,2-dihydropyridine- 3-carbonitrile derivatives 5a-e, 3ʹH-spiro[cyclohexane- 1,2ʹ- thieno[3,2-d]pyrimidin]-3ʹ-yl]phenyl}-2-oxo-4-(substituted phenyl and/or thienyl)-1,2-dihydropyridine-3-carbonitrile derivatives 6a-e, and 4-[(2Z)-3-substituted-arylprop-2-enoyl] phenyl-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidine derivatives 7a-e. Cyclocondensation of 7a-e with hydrazine hydrate produced 6ʹ-(4-chlorophenyl)-3ʹ-[4-(5-substituted aryl-4,5-dihydro- 1H-pyrazol-3-yl)phenyl]-1ʹH-spiro[cyclohexane-1,2ʹ-thieno- [3,2-d]pyrimidin]-4ʹ(3ʹH)-ones 8a-e but with hydroxylamine hydrochloride afforded the corresponding isoxazoline derivatives 9a-e. Also, cyclocondensation by thiourea afforded 2-thioxo-1,2- dihydropyrimidin-4-yl)-phenyl-spiro-{cyclohexanethieno[3,2-d] pyrimidin}-4-one derivatives 10a-e. The new compounds were investigated for antimicrobial activity. Compounds 2c, 8b,c, 9b and 10b were the most potent ones against both Gram-negative and Gram-positive bacteria. Compound 8c exhibited higher antifungal activity towards the examined fungi with MIC of 1-2 μmol mL-1 compared to ketoconazole (MIC 2-3 μmol mL-1 ).

Schlüsselwörter

  • thieno[3,2-d][1,3]oxazin]-4ʹ-one
  • thieno[3,2-d]pyrimidines
  • N-nucleophiles
  • spiro-thieno[3,2-d]pyrimidine
  • ring transformation
  • antimicrobial
Uneingeschränkter Zugang

Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 353 - 372

Zusammenfassung

Abstract

A series of N-(2-(benzoyl/4-chlorobenzoyl)-benzofuran- 3-yl)-2-(substituted)-acetamide derivatives (4a-l, 5a-l) was synthesized in good yield. All synthesized compounds were in agreement with elemental and spectral data. The anticonvulsant activity of all synthesized compounds was assessed against the maximal electroshock induced seizures (MES) model in mice. Neurotoxicity was evaluated using the rotarod method. The majority of compounds exhibited anticonvulsant activity at a dose of 30 mg kg-1 body mass during 0.5-4 h, indicating their ability to prevent seizure spread at low doses. Relative to phenytoin, [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(cyclohexyl( methyl) amino)-acetamide] (5i) and [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-methylpiperidin-1- yl)-acetamide] (5c) demonstrated comparable relative anticonvulsant potency of 0.74 and 0.72, respectively, whereas [(N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-(furan-2-carbonyl)-piperazin-1-yl)-acetamide] (5f) exhibited the lowest relative potency of 0.16. The ALD50 of tested compounds ranged from 1.604 to 1.675 mmol kg-1 body mass. The ED50 of synthesized compounds ranged from 0.055 to 0.259 mmol kg-1 (~23.4 to 127.6 mg kg-1) body mass. The pharmacophore mapping of the examined compounds on standard drugs (phenobarbital, phenytoin, ralitolin and carbamazepine) strongly suggests that these compounds may exert their anticonvulsant activity via the same established mechanism as that of known drugs.

Schlüsselwörter

  • benzofuran
  • anticonvulsant
  • neurotoxicity
  • GABA-AT
  • pharmacophore modeling
  • docking
  • Molegro Virtual Docker 4.0
Uneingeschränkter Zugang

A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 373 - 385

Zusammenfassung

Abstract

Silicon-substituted calcium phosphate (Si-CaP) was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP) cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2) was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future.

Schlüsselwörter

  • heparin
  • carbodiimide
  • rhBMP-2
  • delivery scaffold
  • bone tissue engineering
Uneingeschränkter Zugang

Bioactive chemical constituents of Curcuma longa L. rhizomes extract inhibit the growth of human hepatoma cell line (HepG2)

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 387 - 398

Zusammenfassung

Abstract

The present study was designed to identify the chemical constituents of the methanolic extract of Curcuma longa L. rhizomes and their inhibitory effect on a hepatoma cell line. The methanolic extract was subjected to GC-MS analysis to identify the volatile constituents and the other part of the same extract was subjected to liquid column chromatographic separation to isolate curcumin. The inhibition of cell growth in the hepatoma cell line and the cytopathological changes were studied. GC-MS analysis showed the presence of fifty compounds in the methanolic extract of C. longa. The major compounds were ar-turmerone (20.50 %), β-sesquiphellandrene (5.20 %) and curcumenol (5.11 %). Curcumin was identified using IR, 1H and 13C NMR. The inhibition of cell growth by curcumin (IC50 = 41.69 ± 2.87 μg mL-1) was much more effective than that of methanolic extract (IC50 = 196.12 ± 5.25 μg mL-1). Degenerative and apoptotic changes were more evident in curcumin- treated hepatoma cells than in those treated with the methanol extract. Antitumor potential of the methanolic extract may be attributed to the presence of sesquiterpenes and phenolic constituents including curcumin (0.051 %, 511.39 μg g-1 dried methanol extract) in C. longa rhizomes.

Schlüsselwörter

  • Curcuma longa L.
  • GC-MS analysis
  • curcumin
  • anticancer activity
Uneingeschränkter Zugang

PF573,228 inhibits vascular tumor cell growth, migration as well as angiogenesis, induces apoptosis and abrogates PRAS40 and S6RP phosphorylation

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 399 - 410

Zusammenfassung

Abstract

PF573,228 is a compound that targets focal adhesion kinase (FAK), a non-receptor protein kinase, which is over-expressed in various tumors. The aim of this study was to evaluate the effects of PF573,228 on the cells derived from mouse vascular tumors, namely, endothelioma cells.

The treatment of endothelioma cells with PF573,228 reduced their growth with an IC50 of approximately 4.6 μmol L-1 and inhibited cell migration with an IC50 of about 0.01 μmol L-1. Microscopic studies revealed morphological attributes of apoptosis. These observations were confirmed by ELISA, which showed increased caspase-3 activity. PF573,228 also inhibited angiogenesis in a dose-dependent manner, with an IC50 of approximately 3.7 μmol L-1, and abrogated the phosphorylation of cell survival proteins, proline-rich Akt substrate (PRAS40) and S6 ribosomal protein (S6RP). Array data further revealed that PF573,228 induced caspase-3 activation, thus promoting apoptosis. Since all the processes inhibited by PF573,228 provide important support to tumor survival and progression, the drug may have a potential role in the treatment of vascular tumors.

Schlüsselwörter

  • PF573,228
  • focal adhesion kinase
  • endothelioma
  • apoptosis
  • angiogenesis
Uneingeschränkter Zugang

Olive leaf extract activity against Candida albicans and C. dubliniensis – the in vitro viability study

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 411 - 421

Zusammenfassung

Abstract

Olive leaf extract is characterized by a high content of polyphenols (oleuropein, hydroxytyrosol and their derivatives), which is associated with its therapeutic properties. The objective of the present research was to evaluate the antifungal activity of olive leaf extract against Candida albicans ATCC 10231 and C. dubliniensis CBS 7987 strains. Minimum inhibitory concentrations (MIC) of the extract were determined by several in vitro assays. The extract showed a concentration depended effect on the viability of C. albicans with MIC value of 46.875 mg mL-1 and C. dubliniensis with MIC value 62.5 mg mL-1. Most sensitive methods for testing the antifungal effect of the extracts were the trypan blue exclusion method and fluorescent dye exclusion method while MIC could not be determined by the method according to the EUCAST recommendation suggesting that herbal preparations contain compounds that may interfere with this susceptibility testing. The fluorescent dye exclusion method was also used for the assessment of morphological changes in the nuclei of treated cells. According to the obtained results, olive leaf extract is less effective against the tested strains than hydroxytyrosol, an olive plant constituent tested in our previous study.

Schlüsselwörter

  • antifungal activity
  • Candida albicans
  • Candida dubliniensis
  • olive leaf extract
Uneingeschränkter Zugang

Evaluation of pancreatin stability through enzyme activity determination

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 423 - 431

Zusammenfassung

Abstract

Pancreatin is a biotechnological product containing an enzyme complex, obtained from porcine pancreas, that is employed in treating pancreatic diseases. Experiments regarding the stability of the pharmaceutical formulation containing pancreatin were performed using standard binary mixtures with 6 excipients in a 1:1 ratio (m/m) and a commercial formulation. To accomplish these goals, samples were stored for 1, 3 and 6 months at 40 ± 1 °C and 75 ± 5 % relative humidity (RH) and 40 ± 1 °C and 0 % RH. Stress testing was also performed. All samples were analyzed to evaluate the α-amylase, lipase and protease activities through UV/Vis spectrophotometry. The results revealed that the excipient proprieties and the storage conditions affected enzyme stability. Humidity was a strong influencing factor in the reduction of α-amylase and protease activities. Stress testing indicated that pH 9.0 and UV light did not induce substantial alterations in enzyme activity.

Schlüsselwörter

  • α-amylase
  • lipase
  • protease
  • stress testing
  • pancreatin stability
  • biopharmaceutical
  • UV/VIS spectrophotometry
Uneingeschränkter Zugang

A study of compressibility and compactibility of directly compressible tableting materials containing tramadol hydrochloride

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 433 - 441

Zusammenfassung

Abstract

The paper evaluates and compares the compressibility and compactibility of directly compressible tableting materials for the preparation of hydrophilic gel matrix tablets containing tramadol hydrochloride and the coprocessed dry binders Prosolv® SMCC 90 and Disintequik™ MCC 25. The selected types of hypromellose are Methocel™ Premium K4M and Methocel™ Premium K100M in 30 and 50 % concentrations, the lubricant being magnesium stearate in a 1 % concentration. Compressibility is evaluated by means of the energy profile of compression process and compactibility by the tensile strength of tablets. The values of total energy of compression and plasticity were higher in the tableting materials containing Prosolv® SMCC 90 than in those containing Disintequik™ MCC 25. Tramadol slightly decreased the values of total energy of compression and plasticity. Tableting materials containing Prosolv® SMCC 90 yielded stronger tablets. Tramadol decreased the strength of tablets from both coprocessed dry binders.

Schlüsselwörter

  • tramadol hydrochloride
  • hydrophilic matrix tablets
  • coprocessed dry binder
  • hypromellose
  • energy profile of compression
  • tensile strength of tablets
Uneingeschränkter Zugang

Effect of cerebrolysin on dopaminergic neurodegeneration of rat with oxidative stress induced by 3-nitropropionic acid

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 443 - 448

Zusammenfassung

Abstract

The study tested the hypothesis that cerebrolysin protects the brain from free radicals in rats treated with 3-nitropropionic acid (3-NPA). To address this hypothesis, the levels of dopamine (DA) and some oxidative stress biomarkers were measured after administration of 3-NPA. Young male Fischer rats were treated for three days with cerebrolysin, 3-NPA or both substances. Their brains were extracted, and DA, lipid peroxidation (LP), glutathione (GSH), calcium, and H2O2 were measured using validated methods. In the cortex, hemispheres and cerebellum/medulla oblongata of the group treated with cerebrolysin and 3-NPA, the levels of DA and LP decreased. In addition, calcium and H2O2 levels decreased in the hemispheres of the same group, while GSH increased in cortex. The increased dopamine metabolism due to the administration of cerebrolysin led to increased formation of radical species and oxidative stress, especially when free radicals were generated by 3-NPA.

Schlüsselwörter

  • cerebrolysin
  • dopamine
  • 3-nitropropionic acid
  • oxidative stress
10 Artikel
Uneingeschränkter Zugang

Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 303 - 330

Zusammenfassung

Abstract

Nanoindentation allows quantitative determination of a material’s response to stress such as elastic and plastic deformation or fracture tendency. Key instruments that have enabled great advances in nanomechanical studies are the instrumented nanoindenter and atomic force microscopy. The versatility of these instruments lies in their capability to measure local mechanical response, in very small volumes and depths, while monitoring time, displacement and force with high accuracy and precision.

This review highlights the application of nanoindentation for mechanical characterization of pharmaceutical materials in the preformulation phase (primary investigation of crystalline active ingredients and excipients). With nanoindentation, mechanical response can be assessed with respect to crystal structure. The technique is valuable for mechanical screening of a material at an early development phase in order to predict and better control the processes in which a material is exposed to stress such as milling and compression.

Schlüsselwörter

  • instrumented nanoindentation
  • mechanical properties
  • Young’s modulus
  • indentation hardness
  • fracture toughness
  • crystalline active ingredients and excipients
Uneingeschränkter Zugang

Simple approach to thieno[3,2-d]pyrimidines as new scaffolds of antimicrobial activities

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 331 - 351

Zusammenfassung

Abstract

6ʹ-(4-Chlorophenyl)-spiro[cyclohexane-1,2ʹ-thieno[3,2-d][1,3] oxazin]-4ʹ(1ʹH)-one (1) was synthesized and used as a starting material for the synthesis of a novel series of spiro compounds having biologically active sulfonamide 2a-e and 3ʹ-(4-acetylphenyl)-6ʹ- (4-chlorophenyl)-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d] pyrimidine-4ʹ(3ʹH)-one (3). Compound 2a was used as a key intermediate for the synthesis of sulfonyl carbothioamide derivatives 4a-c. Also, compound 3 was used as an intermediate for the synthesis of 3ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidin]-3ʹ-yl] phenyl}-2-imino-4-(substituted phenyl and/or thienyl)-1,2-dihydropyridine- 3-carbonitrile derivatives 5a-e, 3ʹH-spiro[cyclohexane- 1,2ʹ- thieno[3,2-d]pyrimidin]-3ʹ-yl]phenyl}-2-oxo-4-(substituted phenyl and/or thienyl)-1,2-dihydropyridine-3-carbonitrile derivatives 6a-e, and 4-[(2Z)-3-substituted-arylprop-2-enoyl] phenyl-1ʹH-spiro[cyclohexane-1,2ʹ-thieno[3,2-d]pyrimidine derivatives 7a-e. Cyclocondensation of 7a-e with hydrazine hydrate produced 6ʹ-(4-chlorophenyl)-3ʹ-[4-(5-substituted aryl-4,5-dihydro- 1H-pyrazol-3-yl)phenyl]-1ʹH-spiro[cyclohexane-1,2ʹ-thieno- [3,2-d]pyrimidin]-4ʹ(3ʹH)-ones 8a-e but with hydroxylamine hydrochloride afforded the corresponding isoxazoline derivatives 9a-e. Also, cyclocondensation by thiourea afforded 2-thioxo-1,2- dihydropyrimidin-4-yl)-phenyl-spiro-{cyclohexanethieno[3,2-d] pyrimidin}-4-one derivatives 10a-e. The new compounds were investigated for antimicrobial activity. Compounds 2c, 8b,c, 9b and 10b were the most potent ones against both Gram-negative and Gram-positive bacteria. Compound 8c exhibited higher antifungal activity towards the examined fungi with MIC of 1-2 μmol mL-1 compared to ketoconazole (MIC 2-3 μmol mL-1 ).

Schlüsselwörter

  • thieno[3,2-d][1,3]oxazin]-4ʹ-one
  • thieno[3,2-d]pyrimidines
  • N-nucleophiles
  • spiro-thieno[3,2-d]pyrimidine
  • ring transformation
  • antimicrobial
Uneingeschränkter Zugang

Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 353 - 372

Zusammenfassung

Abstract

A series of N-(2-(benzoyl/4-chlorobenzoyl)-benzofuran- 3-yl)-2-(substituted)-acetamide derivatives (4a-l, 5a-l) was synthesized in good yield. All synthesized compounds were in agreement with elemental and spectral data. The anticonvulsant activity of all synthesized compounds was assessed against the maximal electroshock induced seizures (MES) model in mice. Neurotoxicity was evaluated using the rotarod method. The majority of compounds exhibited anticonvulsant activity at a dose of 30 mg kg-1 body mass during 0.5-4 h, indicating their ability to prevent seizure spread at low doses. Relative to phenytoin, [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(cyclohexyl( methyl) amino)-acetamide] (5i) and [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-methylpiperidin-1- yl)-acetamide] (5c) demonstrated comparable relative anticonvulsant potency of 0.74 and 0.72, respectively, whereas [(N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-(furan-2-carbonyl)-piperazin-1-yl)-acetamide] (5f) exhibited the lowest relative potency of 0.16. The ALD50 of tested compounds ranged from 1.604 to 1.675 mmol kg-1 body mass. The ED50 of synthesized compounds ranged from 0.055 to 0.259 mmol kg-1 (~23.4 to 127.6 mg kg-1) body mass. The pharmacophore mapping of the examined compounds on standard drugs (phenobarbital, phenytoin, ralitolin and carbamazepine) strongly suggests that these compounds may exert their anticonvulsant activity via the same established mechanism as that of known drugs.

Schlüsselwörter

  • benzofuran
  • anticonvulsant
  • neurotoxicity
  • GABA-AT
  • pharmacophore modeling
  • docking
  • Molegro Virtual Docker 4.0
Uneingeschränkter Zugang

A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 373 - 385

Zusammenfassung

Abstract

Silicon-substituted calcium phosphate (Si-CaP) was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP) cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2) was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future.

Schlüsselwörter

  • heparin
  • carbodiimide
  • rhBMP-2
  • delivery scaffold
  • bone tissue engineering
Uneingeschränkter Zugang

Bioactive chemical constituents of Curcuma longa L. rhizomes extract inhibit the growth of human hepatoma cell line (HepG2)

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 387 - 398

Zusammenfassung

Abstract

The present study was designed to identify the chemical constituents of the methanolic extract of Curcuma longa L. rhizomes and their inhibitory effect on a hepatoma cell line. The methanolic extract was subjected to GC-MS analysis to identify the volatile constituents and the other part of the same extract was subjected to liquid column chromatographic separation to isolate curcumin. The inhibition of cell growth in the hepatoma cell line and the cytopathological changes were studied. GC-MS analysis showed the presence of fifty compounds in the methanolic extract of C. longa. The major compounds were ar-turmerone (20.50 %), β-sesquiphellandrene (5.20 %) and curcumenol (5.11 %). Curcumin was identified using IR, 1H and 13C NMR. The inhibition of cell growth by curcumin (IC50 = 41.69 ± 2.87 μg mL-1) was much more effective than that of methanolic extract (IC50 = 196.12 ± 5.25 μg mL-1). Degenerative and apoptotic changes were more evident in curcumin- treated hepatoma cells than in those treated with the methanol extract. Antitumor potential of the methanolic extract may be attributed to the presence of sesquiterpenes and phenolic constituents including curcumin (0.051 %, 511.39 μg g-1 dried methanol extract) in C. longa rhizomes.

Schlüsselwörter

  • Curcuma longa L.
  • GC-MS analysis
  • curcumin
  • anticancer activity
Uneingeschränkter Zugang

PF573,228 inhibits vascular tumor cell growth, migration as well as angiogenesis, induces apoptosis and abrogates PRAS40 and S6RP phosphorylation

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 399 - 410

Zusammenfassung

Abstract

PF573,228 is a compound that targets focal adhesion kinase (FAK), a non-receptor protein kinase, which is over-expressed in various tumors. The aim of this study was to evaluate the effects of PF573,228 on the cells derived from mouse vascular tumors, namely, endothelioma cells.

The treatment of endothelioma cells with PF573,228 reduced their growth with an IC50 of approximately 4.6 μmol L-1 and inhibited cell migration with an IC50 of about 0.01 μmol L-1. Microscopic studies revealed morphological attributes of apoptosis. These observations were confirmed by ELISA, which showed increased caspase-3 activity. PF573,228 also inhibited angiogenesis in a dose-dependent manner, with an IC50 of approximately 3.7 μmol L-1, and abrogated the phosphorylation of cell survival proteins, proline-rich Akt substrate (PRAS40) and S6 ribosomal protein (S6RP). Array data further revealed that PF573,228 induced caspase-3 activation, thus promoting apoptosis. Since all the processes inhibited by PF573,228 provide important support to tumor survival and progression, the drug may have a potential role in the treatment of vascular tumors.

Schlüsselwörter

  • PF573,228
  • focal adhesion kinase
  • endothelioma
  • apoptosis
  • angiogenesis
Uneingeschränkter Zugang

Olive leaf extract activity against Candida albicans and C. dubliniensis – the in vitro viability study

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 411 - 421

Zusammenfassung

Abstract

Olive leaf extract is characterized by a high content of polyphenols (oleuropein, hydroxytyrosol and their derivatives), which is associated with its therapeutic properties. The objective of the present research was to evaluate the antifungal activity of olive leaf extract against Candida albicans ATCC 10231 and C. dubliniensis CBS 7987 strains. Minimum inhibitory concentrations (MIC) of the extract were determined by several in vitro assays. The extract showed a concentration depended effect on the viability of C. albicans with MIC value of 46.875 mg mL-1 and C. dubliniensis with MIC value 62.5 mg mL-1. Most sensitive methods for testing the antifungal effect of the extracts were the trypan blue exclusion method and fluorescent dye exclusion method while MIC could not be determined by the method according to the EUCAST recommendation suggesting that herbal preparations contain compounds that may interfere with this susceptibility testing. The fluorescent dye exclusion method was also used for the assessment of morphological changes in the nuclei of treated cells. According to the obtained results, olive leaf extract is less effective against the tested strains than hydroxytyrosol, an olive plant constituent tested in our previous study.

Schlüsselwörter

  • antifungal activity
  • Candida albicans
  • Candida dubliniensis
  • olive leaf extract
Uneingeschränkter Zugang

Evaluation of pancreatin stability through enzyme activity determination

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 423 - 431

Zusammenfassung

Abstract

Pancreatin is a biotechnological product containing an enzyme complex, obtained from porcine pancreas, that is employed in treating pancreatic diseases. Experiments regarding the stability of the pharmaceutical formulation containing pancreatin were performed using standard binary mixtures with 6 excipients in a 1:1 ratio (m/m) and a commercial formulation. To accomplish these goals, samples were stored for 1, 3 and 6 months at 40 ± 1 °C and 75 ± 5 % relative humidity (RH) and 40 ± 1 °C and 0 % RH. Stress testing was also performed. All samples were analyzed to evaluate the α-amylase, lipase and protease activities through UV/Vis spectrophotometry. The results revealed that the excipient proprieties and the storage conditions affected enzyme stability. Humidity was a strong influencing factor in the reduction of α-amylase and protease activities. Stress testing indicated that pH 9.0 and UV light did not induce substantial alterations in enzyme activity.

Schlüsselwörter

  • α-amylase
  • lipase
  • protease
  • stress testing
  • pancreatin stability
  • biopharmaceutical
  • UV/VIS spectrophotometry
Uneingeschränkter Zugang

A study of compressibility and compactibility of directly compressible tableting materials containing tramadol hydrochloride

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 433 - 441

Zusammenfassung

Abstract

The paper evaluates and compares the compressibility and compactibility of directly compressible tableting materials for the preparation of hydrophilic gel matrix tablets containing tramadol hydrochloride and the coprocessed dry binders Prosolv® SMCC 90 and Disintequik™ MCC 25. The selected types of hypromellose are Methocel™ Premium K4M and Methocel™ Premium K100M in 30 and 50 % concentrations, the lubricant being magnesium stearate in a 1 % concentration. Compressibility is evaluated by means of the energy profile of compression process and compactibility by the tensile strength of tablets. The values of total energy of compression and plasticity were higher in the tableting materials containing Prosolv® SMCC 90 than in those containing Disintequik™ MCC 25. Tramadol slightly decreased the values of total energy of compression and plasticity. Tableting materials containing Prosolv® SMCC 90 yielded stronger tablets. Tramadol decreased the strength of tablets from both coprocessed dry binders.

Schlüsselwörter

  • tramadol hydrochloride
  • hydrophilic matrix tablets
  • coprocessed dry binder
  • hypromellose
  • energy profile of compression
  • tensile strength of tablets
Uneingeschränkter Zugang

Effect of cerebrolysin on dopaminergic neurodegeneration of rat with oxidative stress induced by 3-nitropropionic acid

Online veröffentlicht: 29 Jun 2016
Seitenbereich: 443 - 448

Zusammenfassung

Abstract

The study tested the hypothesis that cerebrolysin protects the brain from free radicals in rats treated with 3-nitropropionic acid (3-NPA). To address this hypothesis, the levels of dopamine (DA) and some oxidative stress biomarkers were measured after administration of 3-NPA. Young male Fischer rats were treated for three days with cerebrolysin, 3-NPA or both substances. Their brains were extracted, and DA, lipid peroxidation (LP), glutathione (GSH), calcium, and H2O2 were measured using validated methods. In the cortex, hemispheres and cerebellum/medulla oblongata of the group treated with cerebrolysin and 3-NPA, the levels of DA and LP decreased. In addition, calcium and H2O2 levels decreased in the hemispheres of the same group, while GSH increased in cortex. The increased dopamine metabolism due to the administration of cerebrolysin led to increased formation of radical species and oxidative stress, especially when free radicals were generated by 3-NPA.

Schlüsselwörter

  • cerebrolysin
  • dopamine
  • 3-nitropropionic acid
  • oxidative stress

Planen Sie Ihre Fernkonferenz mit Scienceendo