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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 3 (September 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

Original Research Paper

Accesso libero

Synthesis of thiophene and N-substituted thieno[3,2-d] pyrimidine derivatives as potent antitumor and antibacterial agents

Pubblicato online: 30 Aug 2017
Pagine: 275 - 292

Astratto

Abstract

A novel series of carbamothioylamino-benzene-sulfonamide-thiophene-carboxylates 4a-c and thieno[3,2-d]pyrimidin-2-yl-amino-benzene-sulfonamides 5a-c were synthesized in a series of synthetic steps and were used as key intermediates for the synthesis of thienotriazolopyrimidine-benzene-sulfonamide derivatives 6a-c and 7a-c. Thieno[3,2-d]pyrimidinones (8 and 9) were also prepared. Compound 9 was used as an intermediate for the synthesis of imidazole/1,2,4-triazole and tetrazine functionalized thieno[3,2-d]pyrimidine derivatives (1012). Pyrrole derivatives/pyrrolopyrimidine/pyrrolotriazolopyrimidine functionalized thiophenes (1519) were also synthesized. Structures of the newly synthesized compounds were established by elemental analysis and spectral data. Most of the newly synthesized compounds were evaluated for their in vitro activity against three human tumor cell lines, namely, liver cancer (HepG-2), colon cancer (HT-29) and lung cancer (NCI-H460), using doxorubicin as standard. Compounds 16 (GI50 = 0.02, 0.04 and 0.06 μmol L−1, resp.) and 19b (GI50 = 0.02, 0.03 and 0.05 μmol L−1, resp.) showed higher activity against all cell lines than doxorubicin. Most of the compounds were also screened for antibacterial activity using ciprofloxacin as standard drug. Compounds 4b and 6b, both containing benzenesulfonamide linked to N-, 10 bearing imidazole moiety, and 15 and 19b,c with a thiophene-2-carboxylic acid chain, exhibited high activity against Gram-positive and Gram-negative bacteria.

Parole chiave

  • thieno[3,2-]pyrimidines
  • thieno[3,2-][1,2,4]triazolo[1,5-]pyrimidines
  • anticancer
  • antibacterial
Accesso libero

Axonal excitability and conduction alterations caused by levobupivacaine in rat

Pubblicato online: 30 Aug 2017
Pagine: 293 - 307

Astratto

Abstract

In this study, effects of the long-acting amide-type local anesthetic levobupivacaine on axonal conduction and excitability parameters of the rat sciatic nerve were thoroughly examined both in vitro and in vivo. In order to deduce its effects on isolated nerve conduction, compound nerve action potential (CNAP) recordings were performed using the suction method over sciatic nerves of Wistar rats before and after administration of 0.05 % (1.7 mmol L−1) levobupivacaine. Levobupivacaine caused complete CNAP area and amplitude depression by blocking conduction in a time-dependent manner.

To assess the influence of levobupivacaine on in vivo excitability properties, threshold-tracking (TT) protocols were performed at sciatic nerves of rats injected with perineural 0.05 % (1.7 mmol L−1) levobupivacaine or vehicle alone. Charge-duration TT results revealed that levobupivacaine increases the rheobase and decreases the strength-duration time constant, suggesting interference of the anesthetic with the opening of Na+ channels. Twenty and 40 % threshold electrotonus curves were found for both groups to follow the same paths, suggesting no significant effect of levobupivacaine on K+ channels for either the fastest or relatively slow conducting fibers. Current-threshold relationship results revealed no significant effect on axonal rectifying channels. However, according to the results of the recovery cycle protocol yielding the pattern of excitability changes following the impulse, potential deviation was found in the recovery characteristics of Na+ channels from the absolute refractory period. Consequently, conduction blockage caused by levobupivacaine may not be due to the passive (capacitive) properties of axon or the conductance of potassium channels but to the decrease in sodium channel conductance.

Parole chiave

  • levobupivacaine
  • nerve conduction
  • excitability
  • threshold electrotonus
Accesso libero

Green ultrasound-assisted three-component click synthesis of novel 1H-1,2,3-triazole carrying benzothiazoles and fluorinated-1,2,4-triazole conjugates and their antimicrobial evaluation

Pubblicato online: 30 Aug 2017
Pagine: 309 - 324

Astratto

Abstract

The present study describes an efficient and ecofriendly, ultrasound, one-pot click cycloaddition approach for the construction of a novel series of 1,4-disubstituted-1,2,3-triazoles tethered with fluorinated 1,2,4-triazole-benzothiazole molecular conjugates. It involved three-component condensation of the appropriate bromoacetamide benzothiazole, sodium azide and 4-alkyl/aryl-5-(2-fluorophenyl)-3-(prop-2-ynylthio)-1,2,4-triazoles 4a-e through a Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction. This approach involves in situ generation of azidoacetamide benzothiazole, followed by condensation with terminal alkynes in the presence of CuSO4/Na-ascorbate in aqueous DMSO under both conventional and ultrasound conditions. Some of the designed 1,2,3-triazole conjugates 6a-o were recognized for their antimicrobial activity against some bacterial and fungal pathogenic strains.

Parole chiave

  • benzothiazoles
  • 1,2,3-triazoles
  • 1,2,4-triazoles
  • click synthesis
  • antimicrobial
Accesso libero

Transdermal delivery of tolterodine tartrate for overactive bladder treatment: In vitro and in vivo evaluation

Pubblicato online: 30 Aug 2017
Pagine: 325 - 339

Astratto

Abstract

The purpose of the study was to develop a transdermal tolterodine tartrate (TT) patch and to analyse its efficacy for overactive bladder (OAB) treatment. Patches were prepared using various polymers and plasticizers via the solvent casting method. The patches were characterized for tensile strength, thickness, moisture content, modulus of elasticity and water absorption capacity. Differential scanning calorimetry and Fourier transform infrared analyses were also performed. To determine patch effectiveness, in vitro release, permeation and animal studies were performed. The patches showed satisfactory percentage of release, up to 89.9 %, and their mechanical properties included thickness (0.10–0.15 mm), tensile strength (4.62–9.98 MPa) and modulus of elasticity (20–29 MPa). There were no significant interactions between TT and other excipients. Animal studies indicated that the TT patch reduced the incidence of side effects; however, studies of longer duration are required to determine the effectiveness in treating OAB.

Parole chiave

  • tolterodine tartrate
  • transdermal
  • overactive bladder
  • matrix patches
  • permeation
Accesso libero

Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds

Pubblicato online: 30 Aug 2017
Pagine: 341 - 355

Astratto

Abstract

This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxy)ethyl] and various substituents on the phenyl ring were demonstrated to affect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules. The degradation profile of the drugs was monitored by spectrophotometry coupled with the multivariate curve resolution technique. Formation of the oxidized pyridine derivative was observed for all the studied DHPs, except for one compound, which showed very fast degradation and formation of a second photo-product. Pharmacological tests on the molecules showed a good muscle relaxing effect, with a mechanism similar to that of nifedipine, however, proving to be more stable to light.

Parole chiave

  • 1,4-dihydropyridine compounds
  • muscle relaxant
  • drug design
  • structure activity relationship
  • photostability
  • MCR analysis
Accesso libero

Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

Pubblicato online: 30 Aug 2017
Pagine: 357 - 371

Astratto

Abstract

In order to investigate the potential of nanostructured lipid carriers for efficient and targeted delivery of curcumin, the pharmacokinetic parameters of curcumin-loaded nanostructured lipid carriers (Cur-NLC) were evaluated in rats after a single intraperitoneal dose of Cur-NLC. In addition, the anticancer activity of Cur-NLC against human lung adenocarcinoma A549 cells was verified by a cellular uptake study, and a cytotoxicity and apoptosis assay. Bioavailability of Cur-NLC was better than that of native curcumin (p > 0.01), as seen from the area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and total plasma clearance (CLz/F). Cur-NLC has a more obvious lung-targeting property in comparison with native curcumin. Cur-NLC showed higher anticancer activity in vitro against A549 cells than native curcumin (IC50 value of 5.66 vs. 9.81 mg L−1, respectively). Meanwhile, Cur-NLC treated A549 cells showed a higher apoptosis rate compared to that of native curcumin. These results indicate that NLC is a promising system for the delivery of curcumin in the treatment of lung adenocarcinoma.

Parole chiave

  • curcumin
  • nanostructured lipid carriers
  • pharmacokinetic
  • anticancer effects
  • lung adenocarcinoma
Accesso libero

Development of a new HPLC method for wogonin in rat plasma: Compatibility of standard and test samples

Pubblicato online: 30 Aug 2017
Pagine: 373 - 384

Astratto

Abstract

In the current paper, an HPLC/UV method was developed and validated for determination of wogonin in plasma. Considerable attention was paid to the preparation of standard samples and factors affecting drug distribution. A preparation procedure was devised to simulate the conditions the drug is expected to experience in vivo while pointing to the shortcomings of previously published methods. The method was validated according to the FDA regulations and showed to be highly efficient and capable of extracting the drug and IS from the plasma accurately and precisely within the specified range of 50–500 ng mL−1. Further, the standard sample preparation of this method can be used as a guideline for other methods, particularly when highly hydrophobic drugs with considerable protein binding are involved and could be valuable in the field of bioanalysis to improve the reliability of methods.

Parole chiave

  • wogonin
  • HPLC/UV
  • standard sample preparation
  • sample compatibility
Accesso libero

Curcumin: Synthesis optimization and in silico interaction with cyclin dependent kinase

Pubblicato online: 30 Aug 2017
Pagine: 385 - 395

Astratto

Abstract

Curcumin is a natural product with enormous biological potential. In this study, curcumin synthesis was revisited using different reaction solvents, a catalyst (n-butylamine) and a water scavenger [(n-BuO)3B], to develop the optimal procedure for its rapid acquisition. During synthesis, solvent choice was found to be an important parameter for better curcumin yield and high purity. In a typical reaction, acetyl acetone was treated with boron trioxide, followed by condensation with vanillin in the presence of tri-n-butyl borate as water scavenger and n-butylamine as catalyst at 80 °C in ethyl acetate to afford curcumin. Moreover, curcumin was also extracted from turmeric powder and spectroscopic properties such as IR, MS, 1H NMR and 13C NMR with synthetic curcumin were established to identify any impurity. The purity of synthetic and extracted curcumin was also checked by TLC and HPLC-DAD. To computationally assess its therapeutic potential against cyclin dependent kinases (CDKs), curcumin was docked in different isoforms of CDKs. It was observed that it did not dock at the active sites of CDK2 and CDK6. However, it could enter into weak interactions with CDK4 protein.

Parole chiave

  • curcumin synthesis
  • CDKs
  • molecular docking

Short Communication

Accesso libero

Influence of novel oral anticoagulants on anticoagulation care management

Pubblicato online: 30 Aug 2017
Pagine: 397 - 406

Astratto

Abstract

Anticoagulation treatment was recently improved by the introduction of novel oral anticoagulants (NOACs). Using a combination of qualitative and quantitative methods, this study explores the effects of the introduction of NOACs on anticoagulation care in Slovenia. Face-to-face interviews with key stakeholders revealed evolvement and challenges of anticoagulation care from different perspectives. Obtained information was further explored through the analysis of nationwide data of drug prescriptions and realization of health care services. Simplified management of anticoagulation treatment with NOACs and their high penetration expanded the capacity of anticoagulation clinics, and consequentially the treated population increased by more than 50 % in the last 5 years. The main challenge concerned the expenditures for medicines, which increased approximately 10 times in just a few years. At the same time, the anticoagulation clinics and their core organisation were not affected, which is not expected to change, since they are vital in delivering high-quality care.

Parole chiave

  • novel oral anticoagulants
  • health care management
  • anticoagulation care
Accesso libero

Pharmacological activities of some triazinopyrazolothieno pyrimidine derivatives

Pubblicato online: 30 Aug 2017
Pagine: 407 - 414

Astratto

Abstract

Triazinopyrazolothieno pyrimidine derivatives 1–5 were evaluated for their anti-inflammatory, analgesic and anticancer activities and acute toxicity. Anti-inflammatory activity of the compounds was studied using the carrageenan test. All tested compounds showed analgesic activity, 3-methoxycarbonyl-4,6-dimethyl-8-[(N-methylindolyl)methyl] pyrimido [5′,4′:4,5]thieno [3′,2′-3,4]pyrazolo [5,1-c]triazine (4) showed activity comparable to that of diclofenac. Compounds 1–5 were also screened for anticancer activity on a human lung cancer cell line (A549) and a human prostate cancer cell line (DU145) using the MTT micro-cultured tetrazolium assay method. Compound 4 showed also significant anticancer activity against both cancer cell lines, comparable to that of doxorubicin. The most active compounds were tested for their acute toxicity and median lethal doses were evaluated.

Parole chiave

  • pyrimidine derivatives
  • triazinopyrazolothieno
  • anti-inflammatory
  • analgesic
  • anticancer
  • acute toxicity
10 Articoli

Original Research Paper

Accesso libero

Synthesis of thiophene and N-substituted thieno[3,2-d] pyrimidine derivatives as potent antitumor and antibacterial agents

Pubblicato online: 30 Aug 2017
Pagine: 275 - 292

Astratto

Abstract

A novel series of carbamothioylamino-benzene-sulfonamide-thiophene-carboxylates 4a-c and thieno[3,2-d]pyrimidin-2-yl-amino-benzene-sulfonamides 5a-c were synthesized in a series of synthetic steps and were used as key intermediates for the synthesis of thienotriazolopyrimidine-benzene-sulfonamide derivatives 6a-c and 7a-c. Thieno[3,2-d]pyrimidinones (8 and 9) were also prepared. Compound 9 was used as an intermediate for the synthesis of imidazole/1,2,4-triazole and tetrazine functionalized thieno[3,2-d]pyrimidine derivatives (1012). Pyrrole derivatives/pyrrolopyrimidine/pyrrolotriazolopyrimidine functionalized thiophenes (1519) were also synthesized. Structures of the newly synthesized compounds were established by elemental analysis and spectral data. Most of the newly synthesized compounds were evaluated for their in vitro activity against three human tumor cell lines, namely, liver cancer (HepG-2), colon cancer (HT-29) and lung cancer (NCI-H460), using doxorubicin as standard. Compounds 16 (GI50 = 0.02, 0.04 and 0.06 μmol L−1, resp.) and 19b (GI50 = 0.02, 0.03 and 0.05 μmol L−1, resp.) showed higher activity against all cell lines than doxorubicin. Most of the compounds were also screened for antibacterial activity using ciprofloxacin as standard drug. Compounds 4b and 6b, both containing benzenesulfonamide linked to N-, 10 bearing imidazole moiety, and 15 and 19b,c with a thiophene-2-carboxylic acid chain, exhibited high activity against Gram-positive and Gram-negative bacteria.

Parole chiave

  • thieno[3,2-]pyrimidines
  • thieno[3,2-][1,2,4]triazolo[1,5-]pyrimidines
  • anticancer
  • antibacterial
Accesso libero

Axonal excitability and conduction alterations caused by levobupivacaine in rat

Pubblicato online: 30 Aug 2017
Pagine: 293 - 307

Astratto

Abstract

In this study, effects of the long-acting amide-type local anesthetic levobupivacaine on axonal conduction and excitability parameters of the rat sciatic nerve were thoroughly examined both in vitro and in vivo. In order to deduce its effects on isolated nerve conduction, compound nerve action potential (CNAP) recordings were performed using the suction method over sciatic nerves of Wistar rats before and after administration of 0.05 % (1.7 mmol L−1) levobupivacaine. Levobupivacaine caused complete CNAP area and amplitude depression by blocking conduction in a time-dependent manner.

To assess the influence of levobupivacaine on in vivo excitability properties, threshold-tracking (TT) protocols were performed at sciatic nerves of rats injected with perineural 0.05 % (1.7 mmol L−1) levobupivacaine or vehicle alone. Charge-duration TT results revealed that levobupivacaine increases the rheobase and decreases the strength-duration time constant, suggesting interference of the anesthetic with the opening of Na+ channels. Twenty and 40 % threshold electrotonus curves were found for both groups to follow the same paths, suggesting no significant effect of levobupivacaine on K+ channels for either the fastest or relatively slow conducting fibers. Current-threshold relationship results revealed no significant effect on axonal rectifying channels. However, according to the results of the recovery cycle protocol yielding the pattern of excitability changes following the impulse, potential deviation was found in the recovery characteristics of Na+ channels from the absolute refractory period. Consequently, conduction blockage caused by levobupivacaine may not be due to the passive (capacitive) properties of axon or the conductance of potassium channels but to the decrease in sodium channel conductance.

Parole chiave

  • levobupivacaine
  • nerve conduction
  • excitability
  • threshold electrotonus
Accesso libero

Green ultrasound-assisted three-component click synthesis of novel 1H-1,2,3-triazole carrying benzothiazoles and fluorinated-1,2,4-triazole conjugates and their antimicrobial evaluation

Pubblicato online: 30 Aug 2017
Pagine: 309 - 324

Astratto

Abstract

The present study describes an efficient and ecofriendly, ultrasound, one-pot click cycloaddition approach for the construction of a novel series of 1,4-disubstituted-1,2,3-triazoles tethered with fluorinated 1,2,4-triazole-benzothiazole molecular conjugates. It involved three-component condensation of the appropriate bromoacetamide benzothiazole, sodium azide and 4-alkyl/aryl-5-(2-fluorophenyl)-3-(prop-2-ynylthio)-1,2,4-triazoles 4a-e through a Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction. This approach involves in situ generation of azidoacetamide benzothiazole, followed by condensation with terminal alkynes in the presence of CuSO4/Na-ascorbate in aqueous DMSO under both conventional and ultrasound conditions. Some of the designed 1,2,3-triazole conjugates 6a-o were recognized for their antimicrobial activity against some bacterial and fungal pathogenic strains.

Parole chiave

  • benzothiazoles
  • 1,2,3-triazoles
  • 1,2,4-triazoles
  • click synthesis
  • antimicrobial
Accesso libero

Transdermal delivery of tolterodine tartrate for overactive bladder treatment: In vitro and in vivo evaluation

Pubblicato online: 30 Aug 2017
Pagine: 325 - 339

Astratto

Abstract

The purpose of the study was to develop a transdermal tolterodine tartrate (TT) patch and to analyse its efficacy for overactive bladder (OAB) treatment. Patches were prepared using various polymers and plasticizers via the solvent casting method. The patches were characterized for tensile strength, thickness, moisture content, modulus of elasticity and water absorption capacity. Differential scanning calorimetry and Fourier transform infrared analyses were also performed. To determine patch effectiveness, in vitro release, permeation and animal studies were performed. The patches showed satisfactory percentage of release, up to 89.9 %, and their mechanical properties included thickness (0.10–0.15 mm), tensile strength (4.62–9.98 MPa) and modulus of elasticity (20–29 MPa). There were no significant interactions between TT and other excipients. Animal studies indicated that the TT patch reduced the incidence of side effects; however, studies of longer duration are required to determine the effectiveness in treating OAB.

Parole chiave

  • tolterodine tartrate
  • transdermal
  • overactive bladder
  • matrix patches
  • permeation
Accesso libero

Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds

Pubblicato online: 30 Aug 2017
Pagine: 341 - 355

Astratto

Abstract

This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxy)ethyl] and various substituents on the phenyl ring were demonstrated to affect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules. The degradation profile of the drugs was monitored by spectrophotometry coupled with the multivariate curve resolution technique. Formation of the oxidized pyridine derivative was observed for all the studied DHPs, except for one compound, which showed very fast degradation and formation of a second photo-product. Pharmacological tests on the molecules showed a good muscle relaxing effect, with a mechanism similar to that of nifedipine, however, proving to be more stable to light.

Parole chiave

  • 1,4-dihydropyridine compounds
  • muscle relaxant
  • drug design
  • structure activity relationship
  • photostability
  • MCR analysis
Accesso libero

Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

Pubblicato online: 30 Aug 2017
Pagine: 357 - 371

Astratto

Abstract

In order to investigate the potential of nanostructured lipid carriers for efficient and targeted delivery of curcumin, the pharmacokinetic parameters of curcumin-loaded nanostructured lipid carriers (Cur-NLC) were evaluated in rats after a single intraperitoneal dose of Cur-NLC. In addition, the anticancer activity of Cur-NLC against human lung adenocarcinoma A549 cells was verified by a cellular uptake study, and a cytotoxicity and apoptosis assay. Bioavailability of Cur-NLC was better than that of native curcumin (p > 0.01), as seen from the area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and total plasma clearance (CLz/F). Cur-NLC has a more obvious lung-targeting property in comparison with native curcumin. Cur-NLC showed higher anticancer activity in vitro against A549 cells than native curcumin (IC50 value of 5.66 vs. 9.81 mg L−1, respectively). Meanwhile, Cur-NLC treated A549 cells showed a higher apoptosis rate compared to that of native curcumin. These results indicate that NLC is a promising system for the delivery of curcumin in the treatment of lung adenocarcinoma.

Parole chiave

  • curcumin
  • nanostructured lipid carriers
  • pharmacokinetic
  • anticancer effects
  • lung adenocarcinoma
Accesso libero

Development of a new HPLC method for wogonin in rat plasma: Compatibility of standard and test samples

Pubblicato online: 30 Aug 2017
Pagine: 373 - 384

Astratto

Abstract

In the current paper, an HPLC/UV method was developed and validated for determination of wogonin in plasma. Considerable attention was paid to the preparation of standard samples and factors affecting drug distribution. A preparation procedure was devised to simulate the conditions the drug is expected to experience in vivo while pointing to the shortcomings of previously published methods. The method was validated according to the FDA regulations and showed to be highly efficient and capable of extracting the drug and IS from the plasma accurately and precisely within the specified range of 50–500 ng mL−1. Further, the standard sample preparation of this method can be used as a guideline for other methods, particularly when highly hydrophobic drugs with considerable protein binding are involved and could be valuable in the field of bioanalysis to improve the reliability of methods.

Parole chiave

  • wogonin
  • HPLC/UV
  • standard sample preparation
  • sample compatibility
Accesso libero

Curcumin: Synthesis optimization and in silico interaction with cyclin dependent kinase

Pubblicato online: 30 Aug 2017
Pagine: 385 - 395

Astratto

Abstract

Curcumin is a natural product with enormous biological potential. In this study, curcumin synthesis was revisited using different reaction solvents, a catalyst (n-butylamine) and a water scavenger [(n-BuO)3B], to develop the optimal procedure for its rapid acquisition. During synthesis, solvent choice was found to be an important parameter for better curcumin yield and high purity. In a typical reaction, acetyl acetone was treated with boron trioxide, followed by condensation with vanillin in the presence of tri-n-butyl borate as water scavenger and n-butylamine as catalyst at 80 °C in ethyl acetate to afford curcumin. Moreover, curcumin was also extracted from turmeric powder and spectroscopic properties such as IR, MS, 1H NMR and 13C NMR with synthetic curcumin were established to identify any impurity. The purity of synthetic and extracted curcumin was also checked by TLC and HPLC-DAD. To computationally assess its therapeutic potential against cyclin dependent kinases (CDKs), curcumin was docked in different isoforms of CDKs. It was observed that it did not dock at the active sites of CDK2 and CDK6. However, it could enter into weak interactions with CDK4 protein.

Parole chiave

  • curcumin synthesis
  • CDKs
  • molecular docking

Short Communication

Accesso libero

Influence of novel oral anticoagulants on anticoagulation care management

Pubblicato online: 30 Aug 2017
Pagine: 397 - 406

Astratto

Abstract

Anticoagulation treatment was recently improved by the introduction of novel oral anticoagulants (NOACs). Using a combination of qualitative and quantitative methods, this study explores the effects of the introduction of NOACs on anticoagulation care in Slovenia. Face-to-face interviews with key stakeholders revealed evolvement and challenges of anticoagulation care from different perspectives. Obtained information was further explored through the analysis of nationwide data of drug prescriptions and realization of health care services. Simplified management of anticoagulation treatment with NOACs and their high penetration expanded the capacity of anticoagulation clinics, and consequentially the treated population increased by more than 50 % in the last 5 years. The main challenge concerned the expenditures for medicines, which increased approximately 10 times in just a few years. At the same time, the anticoagulation clinics and their core organisation were not affected, which is not expected to change, since they are vital in delivering high-quality care.

Parole chiave

  • novel oral anticoagulants
  • health care management
  • anticoagulation care
Accesso libero

Pharmacological activities of some triazinopyrazolothieno pyrimidine derivatives

Pubblicato online: 30 Aug 2017
Pagine: 407 - 414

Astratto

Abstract

Triazinopyrazolothieno pyrimidine derivatives 1–5 were evaluated for their anti-inflammatory, analgesic and anticancer activities and acute toxicity. Anti-inflammatory activity of the compounds was studied using the carrageenan test. All tested compounds showed analgesic activity, 3-methoxycarbonyl-4,6-dimethyl-8-[(N-methylindolyl)methyl] pyrimido [5′,4′:4,5]thieno [3′,2′-3,4]pyrazolo [5,1-c]triazine (4) showed activity comparable to that of diclofenac. Compounds 1–5 were also screened for anticancer activity on a human lung cancer cell line (A549) and a human prostate cancer cell line (DU145) using the MTT micro-cultured tetrazolium assay method. Compound 4 showed also significant anticancer activity against both cancer cell lines, comparable to that of doxorubicin. The most active compounds were tested for their acute toxicity and median lethal doses were evaluated.

Parole chiave

  • pyrimidine derivatives
  • triazinopyrazolothieno
  • anti-inflammatory
  • analgesic
  • anticancer
  • acute toxicity

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