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Dettagli della rivista
Formato
Rivista
eISSN
1846-9558
Pubblicato per la prima volta
28 Feb 2007
Periodo di pubblicazione
4 volte all'anno
Lingue
Inglese

Cerca

Volume 67 (2017): Edizione 4 (December 2017)

Dettagli della rivista
Formato
Rivista
eISSN
1846-9558
Pubblicato per la prima volta
28 Feb 2007
Periodo di pubblicazione
4 volte all'anno
Lingue
Inglese

Cerca

10 Articoli
Accesso libero

Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: physicochemical characterization and in vivo skin performance

Pubblicato online: 11 Jan 2018
Pagine: 415 - 439

Astratto

Abstract

Two types of biocompatible surfactants were evaluated for their capability to formulate skin-friendly/non-irritant microemulsions as vehicles for two poorly water-soluble model drugs differing in properties and concentrations: alkyl polyglucosides (decyl glucoside and caprylyl/capryl glucoside) and ethoxylated surfactants (glycereth-7-caprylate/ caprate and polysorbate 80). Phase behavior, structural inversion and microemulsion solubilization potential for sertaconazole nitrate and adapalene were found to be highly dependent on the surfactants structure and HLB value. Performed characterization (polarized light microscopy, pH, electrical conductivity, rheological, FTIR and DSC measurements) indicated a formulation containing glycereth- 7-caprylate/caprate as suitable for incorporation of both drugs, whereas alkyl polyglucoside-based systems did not exhibit satisfying solubilization capacity for sertaconazole nitrate. Further, monitored parameters were strongly affected by sertaconazole nitrate incorporation, while they remained almost unchanged in adapalene-loaded vehicles. In addition, results of the in vivo skin performance study supported acceptable tolerability for all investigated formulations, suggesting selected microemulsions as promising carriers worth exploring further for effective skin delivery of model drugs.

Parole chiave

  • alkyl polyglucoside
  • ethoxylated surfactant
  • adapalene
  • sertaconazole nitrate
  • biocompatible microemulsion
  • in vivo skin irritation
Accesso libero

Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology

Pubblicato online: 11 Jan 2018
Pagine: 441 - 461

Astratto

Abstract

For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1), entrapment efficiency (Y2) and drug release (Y3). SLMs having a 10-40 μm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV). The obtained outcomes for Y1 (29-86 %), Y2 (45-83 %) and Y3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p < 0.05) affected by lipid concentration. The release mechanism followed Higuchi and zero order models, while n > 0.85 value (Korsmeyer- Peppas) suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

Parole chiave

  • central composite design
  • differential scanning calorimetry
  • solid lipid microparticles
  • microencapsulation
  • nebivolol
  • carnauba wax
Accesso libero

Spectrophotometric method for simultaneous determination of valsartan and substances from the group of statins in binary mixtures

Pubblicato online: 11 Jan 2018
Pagine: 463 - 478

Astratto

Abstract

Applicability of derivative spectrophotometry for the determination of valsartan in the presence of a substance from the group of statins was checked. The obtained results indicate that the proposed method may be effective by using appropriate derivatives: for valsartan and fluvastatin - D1, D2 and D3, for valsartan and pravastatin - D1 and D3, for valsartan and atorvastatin - D2 and D3. The method was characterized by high sensitivity and accuracy. Linearity was maintained in the following ranges: 9.28-32.48 mg mL-1 for valsartan, 8.16-28.56 mg mL-1 f or fluvastatin, 14.40-39.90 mg mL-1 for atorvastatin and 9.60-48.00 mg mL-1 for pravastatin. Determination coefficients were in the range of 0.989-0.999 depending on the analyte and the order of derivative. The precision of the method was high with RSD from 0.1 to 2.5 % and recovery of individual components was within the range of 100 ± 5 %. The developed method was successfully applied to the determination of valsartan combined with fluvastatin, atorvastatin and pravastatin in laboratory prepared mixtures and in pharmaceutical preparations.

Parole chiave

  • valsartan
  • atorvastatin
  • fluvastatin
  • pravastatin
  • derivative spectrophotometry
Accesso libero

Gastroprotective effects of the isopropanol extract of Artemisia princeps and its gastroretentive floating tablets on gastric mucosal injury

Pubblicato online: 11 Jan 2018
Pagine: 479 - 494

Astratto

Abstract

In this study, we investigated the gastroprotective effect of an isopropanol extract from the aerial parts of Artemisia princeps (IPAP) and developed a gastroretentive floating tablet of IPAP (IPAP-FR) for maximized local gastroprotective effects. Pre-treatment with IPAP ameliorated the gastric mucosal hemorrhagic lesions in ethanol/HCl- or indomethacin- treated rats. IPAP decreased mucosal hemorrhage of gastric ulcers induced by ethanol or indomethacin plus pyloric ligation in rats. The optimized floating tablet, IPAP-FR, floated on medium surface with more sustained eupatilin release compared to the non-floating control tablet. X-ray photographs in beagle dogs showed that IPAPFR was retained for > 2 h in the stomach. In the ethanol-induced gastric ulcer rat model, the gastric hemorrhagic lesion was improved more substantially with IPAP-FR compared to the non-floating control tablet. Based on these data, our data suggest that IPAP-FR has an improved therapeutic potential for the treatment of gastric ulcer.

Parole chiave

  • Artemisia princeps Pamp.
  • antiulcer
  • eupatilin
  • floating drug delivery system
  • Xray photographs
Accesso libero

Synthesis and cytotoxicity evaluation of thiazole derivatives obtained from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene- 3-carbonitrile

Pubblicato online: 11 Jan 2018
Pagine: 495 - 510

Astratto

Abstract

Reactivity of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carbonitrile towards thioglycolic acid resulted in thiazole derivative 1. The latter reacted with different chemical reagents to give thiazole, pyrano[2,3-d]thiazole and thiazolo[ 4,5-d]thiazole derivatives. Cytotoxicity effects of the newly synthesized products against six cancer cell lines, namely, human gastric cancer (NUGC), human colon cancer (DLD- 1), human liver cancer (HA22T and HEPG-2), human breast cancer (MCF) and nasopharyngeal carcinoma (HONE-1) as well as against a normal fibroblast cell (WI-38) were evaluated. The study showed that the 4,5,6,7 tetrahydrobenzo[ b] thiophene derivatives 6a, 7, 8a,b, 9b and 10b,c w ere t he most active compounds. Their potencies were attributed to the presence of the electron withdrawing groups.

Parole chiave

  • tetrahydrobenzo[b]thiophene
  • thiazole
  • pyrano[ 2,3-d]thiazole
  • thiazolo[4,5-d]thiazole
  • cytotoxicity
  • anticancer activity
Accesso libero

Solving manufacturing problems for L-carnitine-L-tartrate to improve the likelihood of successful product scale-up

Pubblicato online: 11 Jan 2018
Pagine: 511 - 525

Astratto

Abstract

L-carnitine-L-tartrate, a non-essential amino acid, is hygroscopic. This causes a problem in tablet production due to pronounced adhesion of tablets to punches. A 33 full factorial design was adopted to suggest a tablet formulation. Three adsorbents were suggested (Aerosil 200, Aerosil R972, talc) to reduce stickiness at three concentrations (1, 3 and 5 %), and three fillers (mannitol, Avicel PH 101, Dibasic calcium phosphate) were chosen to prepare 27 formulations. Micromeritic properties of formulations were studied, and tablets were prepared by wet granulation. Absence of picking, sticking or capping, recording of sufficient hardness, acceptable friability and tablet ejection force indicated formulation success. The resulting formulation prepared using Avicel PH 101 and 1 % Aerosil 200 was submitted to further investigation in order to choose the most suitable compression conditions using a 33 full factorial design. Variables included compression force, tableting rate and magnesium stearate (lubricant) concentration. The formulation prepared at compression force of 25 kN, using 2 % magnesium stearate, at a production rate of 30 tablets/ minute, was found to be the most appropriate scale up candidate.

Parole chiave

  • L-carnitine-L-tartrate
  • adsorbent
  • scale-up
  • compression force
  • ejection force
  • hygroscopic
Accesso libero

Synthesis and evaluation of antitumor activity of new 4-substituted thieno[3,2-d]pyrimidine and thienotriazolopyrimidine derivatives

Pubblicato online: 11 Jan 2018
Pagine: 527 - 542

Astratto

Abstract

3-Methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[3,2-d]pyrimidin- 4(1H)-one (2), on treatment with phosphorous oxychoride, affored 4-chloro-3-methyl-6-phenyl -thieno[3,2-d]pyrimidine- 2(3H)-thione (3). A series of novel 6-phenyl-thieno[3,2-d]pyrimidine derivatives 4-9 bearing different functional groups were synthesized via treatment of compound 3 with different reagents. On the other hand, compound 2 was used to synthesize ethyl-[(3-methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[ 3,2-d]pyrimidin-4-yl)-oxy]acetate (10), 2-hydrazinyl- -3-methyl-6-phenyl-thieno[3,2-d]pyrimidin-4(3H)-one (11), 3-methyl-2-(methyl-sulfanyl)-6-phenyl-thieno[3,2-d]pyrimidin- 4(3H)-one (12) and N-(phenyl)/4-chlorophenyl or methoxy- phenyl)-2-[(3-methyl-4-oxo-6-phenyl-3,4-dihydrothieno[ 3,2-d]pyrimidin-2-yl)-sulfanyl]-acetamide (13a-c). In addition, compound 12 was used to synthesize thieno[1,2,4] triazolopyrimidine derivatives 14 and 15 and 3-methyl-2-(methyl-sulfonyl)-6-phenyl-thieno[3,2-d]pyrimidin-4(3H)-one (16) through the reaction with the respective reagents. Moreover, the reaction of 16 with 4-phenylenediamine gave 2-[(4-aminophenyl)-amino]-3-methyl-6-phenyl-thieno[3,2-d] pyrimidin-4(3H)-one (17), which reacted with methanesulfonyl chloride to afford N-{4-[(3-methyl-4-oxo-6-phenyl-3H,4H- -thieno[3,2-d]pyrimidin-2-yl)-amino]phenyl}-methanesulfonamide (18). The majority of the newly synthesized compounds displayed potent anticancer activity, comparable to that of doxorubicin, on three human cancer cell lines, including the human breast adenocarcinoma cell line (MCF-7), cervical carcinoma cell line (HeLa) and colonic carcinoma cell line (HCT- 116). Compounds 18, 13b and 10 were nearly as active as doxorubicin whereas compounds 6, 7b and 15 exhibited marked growth inhibition, but still lower than doxorubicin.

Parole chiave

  • thieno[3,2-d]pyrimidines
  • thienotriazolopyrimidine derivatives
  • antitumor activity
Accesso libero

Evaluation of immunomodulatory effects of lamotrigine in BALB/c mice

Pubblicato online: 11 Jan 2018
Pagine: 543 - 555

Astratto

Abstract

Modulation of the immune system has recently been shown to be involved in the pharmacological effects of old antiepileptic drugs and in the pathogenesis of epilepsy. Therefore, the most recent guidelines for immunotoxicological evaluation of drugs were consulted to investigate the immunomodulatory effects of lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in vivo effects of lamotrigine on delayed-type hypersensitivity (DTH) response to sheep red blood cell (SRBC) antigens, hemagglutination titer assays and hematological changes. In vitro effects of lamotrigine on ConA-induced splenocyte proliferation and cytokine secretion were assessed. The results showed that lamotrigine treatment significantly increased the DTH response to SRBC in the mouse model of this study. This was accompanied by a significant increase in relative monocyte and neutrophil counts and in spleen cellularity. Lamotrigine significantly inhibited ConA-induced splenocyte proliferation in vitro and it significantly inhibited IL-2 and TNF-α secretion in ConA-stimulated splenocytes. In conclusion, the results demonstrated significant immunomodulatory effects of lamotrigine in BALB/c mice. These data could expand the understanding of lamotrigine-induced adverse reactions and its role in modulating the immune system in epilepsy.

Parole chiave

  • lamotrigine
  • epilepsy
  • cytokine
  • hypersensitivity
  • immunomodulatory effect
  • immunotoxicity
Accesso libero

A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi

Pubblicato online: 11 Jan 2018
Pagine: 557 - 567

Astratto

Abstract

In this study, the effect of four xyloketals 1-4 on store-operated calcium entry (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual ketal with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals penetrated easily through the cell membrane. Moreover, the molecular docking study of xyloketal A with activation region of the stromal interaction molecule (STIM) 1 and the calcium release-activated calcium modulator (ORAI) 1 (STIM1-ORAI1) protein complex, the key domain of SOCE, revealed that xyloketal A exhibited a noncovalent interaction with the key residue lysine 363 (LYS363) in the identified cytosolic regions in STIM1-C. These findings provided useful information about xyloketal A as a SOCE inhibitor for further evaluation.

Parole chiave

  • xyloketal A
  • store-operated calcium entry
  • molecular docking
  • IL-8
  • parallel artificial membrane permeability assay
Accesso libero

Influence of plasma on the physical properties of ointments with quercetin

Pubblicato online: 11 Jan 2018
Pagine: 569 - 578

Astratto

Abstract

Effects of two independent variables - the content of quercetin (0 or 1 or 1.5 or 5 %) and the content of plasma (0 or 2 or 4 or 6 %) - on the organoleptic properties and rheological parameters of model formulations prepared on an amphiphilic base were estimated. The consistency of all ointments was uniform, and the content of quercetin and plasma lay within the predefined range. Tested ointments are non-Newtonian systems. The content of quercetin and plasma was found to have a significant effect on the rheological properties of the ointments. An increase in the content of plasma in ointments was accompanied by a significant increase in their hardness, viscosity and shear stress and a reduction of their spreadability. The best rheological properties were shown by formulation F-3, containing 1.5 % of quercetin and 2 % of plasma.

Parole chiave

  • quercetin
  • plasma
  • ointment
  • rheological property
10 Articoli
Accesso libero

Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: physicochemical characterization and in vivo skin performance

Pubblicato online: 11 Jan 2018
Pagine: 415 - 439

Astratto

Abstract

Two types of biocompatible surfactants were evaluated for their capability to formulate skin-friendly/non-irritant microemulsions as vehicles for two poorly water-soluble model drugs differing in properties and concentrations: alkyl polyglucosides (decyl glucoside and caprylyl/capryl glucoside) and ethoxylated surfactants (glycereth-7-caprylate/ caprate and polysorbate 80). Phase behavior, structural inversion and microemulsion solubilization potential for sertaconazole nitrate and adapalene were found to be highly dependent on the surfactants structure and HLB value. Performed characterization (polarized light microscopy, pH, electrical conductivity, rheological, FTIR and DSC measurements) indicated a formulation containing glycereth- 7-caprylate/caprate as suitable for incorporation of both drugs, whereas alkyl polyglucoside-based systems did not exhibit satisfying solubilization capacity for sertaconazole nitrate. Further, monitored parameters were strongly affected by sertaconazole nitrate incorporation, while they remained almost unchanged in adapalene-loaded vehicles. In addition, results of the in vivo skin performance study supported acceptable tolerability for all investigated formulations, suggesting selected microemulsions as promising carriers worth exploring further for effective skin delivery of model drugs.

Parole chiave

  • alkyl polyglucoside
  • ethoxylated surfactant
  • adapalene
  • sertaconazole nitrate
  • biocompatible microemulsion
  • in vivo skin irritation
Accesso libero

Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology

Pubblicato online: 11 Jan 2018
Pagine: 441 - 461

Astratto

Abstract

For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1), entrapment efficiency (Y2) and drug release (Y3). SLMs having a 10-40 μm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV). The obtained outcomes for Y1 (29-86 %), Y2 (45-83 %) and Y3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p < 0.05) affected by lipid concentration. The release mechanism followed Higuchi and zero order models, while n > 0.85 value (Korsmeyer- Peppas) suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

Parole chiave

  • central composite design
  • differential scanning calorimetry
  • solid lipid microparticles
  • microencapsulation
  • nebivolol
  • carnauba wax
Accesso libero

Spectrophotometric method for simultaneous determination of valsartan and substances from the group of statins in binary mixtures

Pubblicato online: 11 Jan 2018
Pagine: 463 - 478

Astratto

Abstract

Applicability of derivative spectrophotometry for the determination of valsartan in the presence of a substance from the group of statins was checked. The obtained results indicate that the proposed method may be effective by using appropriate derivatives: for valsartan and fluvastatin - D1, D2 and D3, for valsartan and pravastatin - D1 and D3, for valsartan and atorvastatin - D2 and D3. The method was characterized by high sensitivity and accuracy. Linearity was maintained in the following ranges: 9.28-32.48 mg mL-1 for valsartan, 8.16-28.56 mg mL-1 f or fluvastatin, 14.40-39.90 mg mL-1 for atorvastatin and 9.60-48.00 mg mL-1 for pravastatin. Determination coefficients were in the range of 0.989-0.999 depending on the analyte and the order of derivative. The precision of the method was high with RSD from 0.1 to 2.5 % and recovery of individual components was within the range of 100 ± 5 %. The developed method was successfully applied to the determination of valsartan combined with fluvastatin, atorvastatin and pravastatin in laboratory prepared mixtures and in pharmaceutical preparations.

Parole chiave

  • valsartan
  • atorvastatin
  • fluvastatin
  • pravastatin
  • derivative spectrophotometry
Accesso libero

Gastroprotective effects of the isopropanol extract of Artemisia princeps and its gastroretentive floating tablets on gastric mucosal injury

Pubblicato online: 11 Jan 2018
Pagine: 479 - 494

Astratto

Abstract

In this study, we investigated the gastroprotective effect of an isopropanol extract from the aerial parts of Artemisia princeps (IPAP) and developed a gastroretentive floating tablet of IPAP (IPAP-FR) for maximized local gastroprotective effects. Pre-treatment with IPAP ameliorated the gastric mucosal hemorrhagic lesions in ethanol/HCl- or indomethacin- treated rats. IPAP decreased mucosal hemorrhage of gastric ulcers induced by ethanol or indomethacin plus pyloric ligation in rats. The optimized floating tablet, IPAP-FR, floated on medium surface with more sustained eupatilin release compared to the non-floating control tablet. X-ray photographs in beagle dogs showed that IPAPFR was retained for > 2 h in the stomach. In the ethanol-induced gastric ulcer rat model, the gastric hemorrhagic lesion was improved more substantially with IPAP-FR compared to the non-floating control tablet. Based on these data, our data suggest that IPAP-FR has an improved therapeutic potential for the treatment of gastric ulcer.

Parole chiave

  • Artemisia princeps Pamp.
  • antiulcer
  • eupatilin
  • floating drug delivery system
  • Xray photographs
Accesso libero

Synthesis and cytotoxicity evaluation of thiazole derivatives obtained from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene- 3-carbonitrile

Pubblicato online: 11 Jan 2018
Pagine: 495 - 510

Astratto

Abstract

Reactivity of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carbonitrile towards thioglycolic acid resulted in thiazole derivative 1. The latter reacted with different chemical reagents to give thiazole, pyrano[2,3-d]thiazole and thiazolo[ 4,5-d]thiazole derivatives. Cytotoxicity effects of the newly synthesized products against six cancer cell lines, namely, human gastric cancer (NUGC), human colon cancer (DLD- 1), human liver cancer (HA22T and HEPG-2), human breast cancer (MCF) and nasopharyngeal carcinoma (HONE-1) as well as against a normal fibroblast cell (WI-38) were evaluated. The study showed that the 4,5,6,7 tetrahydrobenzo[ b] thiophene derivatives 6a, 7, 8a,b, 9b and 10b,c w ere t he most active compounds. Their potencies were attributed to the presence of the electron withdrawing groups.

Parole chiave

  • tetrahydrobenzo[b]thiophene
  • thiazole
  • pyrano[ 2,3-d]thiazole
  • thiazolo[4,5-d]thiazole
  • cytotoxicity
  • anticancer activity
Accesso libero

Solving manufacturing problems for L-carnitine-L-tartrate to improve the likelihood of successful product scale-up

Pubblicato online: 11 Jan 2018
Pagine: 511 - 525

Astratto

Abstract

L-carnitine-L-tartrate, a non-essential amino acid, is hygroscopic. This causes a problem in tablet production due to pronounced adhesion of tablets to punches. A 33 full factorial design was adopted to suggest a tablet formulation. Three adsorbents were suggested (Aerosil 200, Aerosil R972, talc) to reduce stickiness at three concentrations (1, 3 and 5 %), and three fillers (mannitol, Avicel PH 101, Dibasic calcium phosphate) were chosen to prepare 27 formulations. Micromeritic properties of formulations were studied, and tablets were prepared by wet granulation. Absence of picking, sticking or capping, recording of sufficient hardness, acceptable friability and tablet ejection force indicated formulation success. The resulting formulation prepared using Avicel PH 101 and 1 % Aerosil 200 was submitted to further investigation in order to choose the most suitable compression conditions using a 33 full factorial design. Variables included compression force, tableting rate and magnesium stearate (lubricant) concentration. The formulation prepared at compression force of 25 kN, using 2 % magnesium stearate, at a production rate of 30 tablets/ minute, was found to be the most appropriate scale up candidate.

Parole chiave

  • L-carnitine-L-tartrate
  • adsorbent
  • scale-up
  • compression force
  • ejection force
  • hygroscopic
Accesso libero

Synthesis and evaluation of antitumor activity of new 4-substituted thieno[3,2-d]pyrimidine and thienotriazolopyrimidine derivatives

Pubblicato online: 11 Jan 2018
Pagine: 527 - 542

Astratto

Abstract

3-Methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[3,2-d]pyrimidin- 4(1H)-one (2), on treatment with phosphorous oxychoride, affored 4-chloro-3-methyl-6-phenyl -thieno[3,2-d]pyrimidine- 2(3H)-thione (3). A series of novel 6-phenyl-thieno[3,2-d]pyrimidine derivatives 4-9 bearing different functional groups were synthesized via treatment of compound 3 with different reagents. On the other hand, compound 2 was used to synthesize ethyl-[(3-methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[ 3,2-d]pyrimidin-4-yl)-oxy]acetate (10), 2-hydrazinyl- -3-methyl-6-phenyl-thieno[3,2-d]pyrimidin-4(3H)-one (11), 3-methyl-2-(methyl-sulfanyl)-6-phenyl-thieno[3,2-d]pyrimidin- 4(3H)-one (12) and N-(phenyl)/4-chlorophenyl or methoxy- phenyl)-2-[(3-methyl-4-oxo-6-phenyl-3,4-dihydrothieno[ 3,2-d]pyrimidin-2-yl)-sulfanyl]-acetamide (13a-c). In addition, compound 12 was used to synthesize thieno[1,2,4] triazolopyrimidine derivatives 14 and 15 and 3-methyl-2-(methyl-sulfonyl)-6-phenyl-thieno[3,2-d]pyrimidin-4(3H)-one (16) through the reaction with the respective reagents. Moreover, the reaction of 16 with 4-phenylenediamine gave 2-[(4-aminophenyl)-amino]-3-methyl-6-phenyl-thieno[3,2-d] pyrimidin-4(3H)-one (17), which reacted with methanesulfonyl chloride to afford N-{4-[(3-methyl-4-oxo-6-phenyl-3H,4H- -thieno[3,2-d]pyrimidin-2-yl)-amino]phenyl}-methanesulfonamide (18). The majority of the newly synthesized compounds displayed potent anticancer activity, comparable to that of doxorubicin, on three human cancer cell lines, including the human breast adenocarcinoma cell line (MCF-7), cervical carcinoma cell line (HeLa) and colonic carcinoma cell line (HCT- 116). Compounds 18, 13b and 10 were nearly as active as doxorubicin whereas compounds 6, 7b and 15 exhibited marked growth inhibition, but still lower than doxorubicin.

Parole chiave

  • thieno[3,2-d]pyrimidines
  • thienotriazolopyrimidine derivatives
  • antitumor activity
Accesso libero

Evaluation of immunomodulatory effects of lamotrigine in BALB/c mice

Pubblicato online: 11 Jan 2018
Pagine: 543 - 555

Astratto

Abstract

Modulation of the immune system has recently been shown to be involved in the pharmacological effects of old antiepileptic drugs and in the pathogenesis of epilepsy. Therefore, the most recent guidelines for immunotoxicological evaluation of drugs were consulted to investigate the immunomodulatory effects of lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in vivo effects of lamotrigine on delayed-type hypersensitivity (DTH) response to sheep red blood cell (SRBC) antigens, hemagglutination titer assays and hematological changes. In vitro effects of lamotrigine on ConA-induced splenocyte proliferation and cytokine secretion were assessed. The results showed that lamotrigine treatment significantly increased the DTH response to SRBC in the mouse model of this study. This was accompanied by a significant increase in relative monocyte and neutrophil counts and in spleen cellularity. Lamotrigine significantly inhibited ConA-induced splenocyte proliferation in vitro and it significantly inhibited IL-2 and TNF-α secretion in ConA-stimulated splenocytes. In conclusion, the results demonstrated significant immunomodulatory effects of lamotrigine in BALB/c mice. These data could expand the understanding of lamotrigine-induced adverse reactions and its role in modulating the immune system in epilepsy.

Parole chiave

  • lamotrigine
  • epilepsy
  • cytokine
  • hypersensitivity
  • immunomodulatory effect
  • immunotoxicity
Accesso libero

A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi

Pubblicato online: 11 Jan 2018
Pagine: 557 - 567

Astratto

Abstract

In this study, the effect of four xyloketals 1-4 on store-operated calcium entry (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual ketal with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals penetrated easily through the cell membrane. Moreover, the molecular docking study of xyloketal A with activation region of the stromal interaction molecule (STIM) 1 and the calcium release-activated calcium modulator (ORAI) 1 (STIM1-ORAI1) protein complex, the key domain of SOCE, revealed that xyloketal A exhibited a noncovalent interaction with the key residue lysine 363 (LYS363) in the identified cytosolic regions in STIM1-C. These findings provided useful information about xyloketal A as a SOCE inhibitor for further evaluation.

Parole chiave

  • xyloketal A
  • store-operated calcium entry
  • molecular docking
  • IL-8
  • parallel artificial membrane permeability assay
Accesso libero

Influence of plasma on the physical properties of ointments with quercetin

Pubblicato online: 11 Jan 2018
Pagine: 569 - 578

Astratto

Abstract

Effects of two independent variables - the content of quercetin (0 or 1 or 1.5 or 5 %) and the content of plasma (0 or 2 or 4 or 6 %) - on the organoleptic properties and rheological parameters of model formulations prepared on an amphiphilic base were estimated. The consistency of all ointments was uniform, and the content of quercetin and plasma lay within the predefined range. Tested ointments are non-Newtonian systems. The content of quercetin and plasma was found to have a significant effect on the rheological properties of the ointments. An increase in the content of plasma in ointments was accompanied by a significant increase in their hardness, viscosity and shear stress and a reduction of their spreadability. The best rheological properties were shown by formulation F-3, containing 1.5 % of quercetin and 2 % of plasma.

Parole chiave

  • quercetin
  • plasma
  • ointment
  • rheological property

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