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Detalles de la revista
Formato
Revista
eISSN
1846-9558
Publicado por primera vez
28 Feb 2007
Periodo de publicación
4 veces al año
Idiomas
Inglés

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

Detalles de la revista
Formato
Revista
eISSN
1846-9558
Publicado por primera vez
28 Feb 2007
Periodo de publicación
4 veces al año
Idiomas
Inglés

Buscar

10 Artículos
Acceso abierto

Core-shell nanofibers as drug delivery systems

Publicado en línea: 28 Mar 2019
Páginas: 131 - 153

Resumen

Abstract

Core-shell nanofibers have grown in popularity over the last decade owing to their special features and their many applications in biomedicine. They can be produced by electrospinning of immiscible polymer blends or emulsions through a single nozzle or by electrospinning using a coaxial nozzle. Several of the electrospinning parameters allow great versatility for the compositions and diameters of core-shell nanofibers to be produced. Morphology of core-shell nanofibers can be investigated using transmission electron microscopy and, in some cases, scanning electron microscopy. Several studies have shown that core-shell nanofibers have some advantages over monolithic nanofibers, such as better drug, protein, gene or probiotic incorporation into the nanofibers, greater control over drug release, and maintenance of protein structure and activity during electrospinning. We herein review the production and characterization of core-shell nanofibers, the critical parameters that affect their development, and their advantages as delivery systems.

Palabras clave

  • coaxial electrospinning
  • emulsion electrospinning
  • core-shell nanofibers
  • nanotechnology
  • nanodelivery system
  • drug release
Acceso abierto

How to assess orodispersible film quality? A review of applied methods and their modifications

Publicado en línea: 28 Mar 2019
Páginas: 155 - 176

Resumen

Abstract

In recent years, there has been a tendency toward creating innovative, easy to use and patient-friendly drug delivery systems suitable for every consumer profile, which would ensure safety, stability and acceptability of a drug. One of the relatively novel and promising approaches is the manufacture of orodispersible films (ODFs), which is an upcoming area of interest in drug delivery. They are defined as polymer thin films that disintegrate in the oral cavity within seconds, without drinking water or chewing, and eliminate the risk of choking. Gaining special usefulness in therapies of children and the elderly, ODFs seem to fill the gap in the range of preparations available for these groups of patients. As no detailed monography of ODFs including testing methods and uniform requirements has been presented in any of the pharmacopoeias to date, the aim of this article is to give an overview of the applied testing methods, their modifications and innovative approaches related to ODF quality assessment.

Palabras clave

  • orodispersible film
  • quality assessment
  • ODF testing methods
  • mechanical properties
  • disintegration time
Acceso abierto

Chemistry and pharmacological diversity of quinoxaline motifs as anticancer agents

Publicado en línea: 28 Mar 2019
Páginas: 177 - 196

Resumen

Abstract

Surpassing heart diseases, cancer is taking the lead as the deadliest disease because of its fast rate of spreading in all parts of the world. Tireless commitment to searching for novel therapeutic medicines is a worthwhile adventure in synthetic chemistry because of the drug resistance predicament and regular outbreak of new diseases due to abnormal cell growth and proliferation. Medicinal chemistry researchers and pharmacists have unveiled quinoxaline templates as precursors of importance and valuable intermediates in drug discovery because they have been established to possess diverse pharmacological potentials. Hence, this review highlights the current versatile routes to accessing functionalized quinoxaline motifs and harnessing their documented therapeutic potentials for anticancer drug development.

Palabras clave

  • quinoxaline
  • anticancer activity
  • pharmacophore
Acceso abierto

Transdermal patches: Design and current approaches to painless drug delivery

Publicado en línea: 28 Mar 2019
Páginas: 197 - 215

Resumen

Abstract

Use of transdermal patches can evade many issues associated with oral drug delivery, such as first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acidic media, drug fluctuations, and gastrointestinal irritation. This article reviews various transdermal patches available in the market, types, structural components, polymer role, and the required assessment tools. Although transdermal patches have medical applications for smoking cessation, pain relief, osteoporosis, contraception, motion sickness, angina pectoris, and cardiac disorders, advances in formulation development are ongoing to make transdermal patches capable of delivering more challenging drugs. Transdermal patches can be tailored and developed according to the physicochemical properties of active and inactive components, and applicability for long-term use. Therefore, a number of chemical approaches and physical techniques for transdermal patch development are under investigation.

Palabras clave

  • transdermal patch
  • transdermal drug delivery
  • polymer matrix
  • adhesives
  • skin formulation
Acceso abierto

Quantitative analysis and resolution of pharmaceuticals in the environment using multivariate curve resolution-alternating least squares (MCR-ALS)

Publicado en línea: 28 Mar 2019
Páginas: 217 - 231

Resumen

Abstract

The study presents the application of multivariate curve resolution alternating least squares (MCR-ALS) with a correlation constraint for simultaneous resolution and quantification of ketoprofen, naproxen, paracetamol and caffeine as target analytes and triclosan as an interfering component in different water samples using UV-Vis spectrophotometric data. A multivariate regression model using the partial least squares regression (PLSR) algorithm was developed and calculated. The MCR-ALS results were compared with the PLSR obtained results. Both models were validated on external sample sets and were applied to the analysis of real water samples. Both models showed comparable and satisfactory results with the relative error of prediction of real water samples in the range of 1.70–9.75 % and 1.64–9.43 % for MCR-ALS and PLSR, resp. The obtained results show the potential of MCR-ALS with correlation constraint to be applied for the determination of different pharmaceuticals in complex environmental matrices.

Palabras clave

  • multivariate curve resolution alternating least squares
  • correlation constraint
  • partial least squares
  • multivariate calibration
  • environmental analysis
  • UV-Vis spectrophotometry
Acceso abierto

Synthesis and antiplasmodial evaluation of novel mefloquine-based fumardiamides

Publicado en línea: 28 Mar 2019
Páginas: 233 - 248

Resumen

Abstract

The paper is focused on the synthesis and screening of the antiplasmodial activity of novel fumardiamides 5–10 with the mefloquine pharmacophore and a Michael acceptor motif. Multi-step reactions leading to the title compounds included two amide bond formations. The first amide bond was achieved by the reaction of (E)-ethyl 4-chloro-4-oxobut-2-enoate (1) and N1-(2,8-bis(trifluoromethyl)quinolin-4-yl) butane-1,4-diamine (2). The obtained ester 3 was hydrolyzed and gave acid 4, which then reacted with the selected halogenanilines in the presence of HATU/DIEA and formed products 5–10. Title compounds showed marked, dose dependent activity in vitro against hepatic stages of Plasmodium berghei. IC50 values of the most active compounds 5, 7 and 9 bearing 3-fluoro, 3-chloro and 3-trifluoromethyl substituents were 3.04–4.16 µmol L−1, respectively. On the other hand, the compounds exerted only weak activity against the erythrocytic stages of two P. falciparum strains (Pf3D7 and PfDd2) in vitro, with the exception of compound 5 (IC50 = 2.9 µmol L−1).

Palabras clave

  • mefloquine
  • 2,8-bis(trifluoromethyl)quinoline
  • fumardiamide
  • halogenaniline
  • antiplasmodial activity
Acceso abierto

Stability-indicating HPLC-PDA assay for simultaneous determination of paracetamol, thiamine and pyridoxal phosphate in tablet formulations

Publicado en línea: 28 Mar 2019
Páginas: 249 - 259

Resumen

Abstract

With the increased number of multi-drug formulations, there is a need to develop new methods for simultaneous determinations of drugs. A precise, accurate and reliable liquid chromatographic method was developed for simultaneous determination of paracetamol, thiamine, and pyridoxal phosphate in pharmaceutical formulations. Separation of analytes was carried out with an Agilent Poroshell C18 column. A mixture of ammonium phosphate buffer (pH = 3.0), acetonitrile and methanol in the ratio of 86:7:7 (V/V/V) was used as the mobile phase pumped at a flow rate of 1.8 mL min−1. Detection of all three components, impurities and degradation products was performed at the selected wavelength of 270 nm. The developed method was validated in terms of linearity, specificity, precision, accuracy, LOD and LOQ as per ICH guidelines. Linearity of the developed method was found in the range 17.5–30 µg mL−1 for thiamine, 35–60 µg mL−1 for pyridoxal phosphate and 87.5–150 µg mL−1 for paracetamol. The coefficient of determination was ≥ 0.9981 for all three analytes. The proposed HPLC method was found to be simple and reliable for the routine simultaneous analysis of paracetamol, thiamine and pyridoxal phosphate in tablet formulations. Complete separation of analytes in the presence of degradation products indicated selectivity of the method.

Palabras clave

  • paracetamol
  • thiamine
  • pyridoxine phosphate
  • degradation
  • HPLC-PDA
Acceso abierto

Synthesis and evaluation of some new 1,3,4-oxadiazoles bearing thiophene, thiazole, coumarin, pyridine and pyridazine derivatives as antiviral agents

Publicado en línea: 28 Mar 2019
Páginas: 261 - 276

Resumen

Abstract

In an attempt to produce heterocyclic compounds based on 1,3,4-oxadiazole derivatives with potential antiviral activity, synthesis of compound 1 [2-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile] was performed through the reaction of cyanoacetic acid hydrazide with carbon disulfide in alcoholic potassium hydroxide. Compound 1 has an activating methylene group, so it was directed toward some specific reactions. Thus, aryldiazonium chlorides reacted with compound 1 affording hydrazono derivatives 2a-c. Also, aromatic aldehydes reacted with compound 1 to produce compounds 3a,b. Furthermore, cyclic ketones were subjected to the synthesis of fused thiophene derivatives 4a,bvia reaction with compound 1 in the presence of elemental sulfur. In addition, 1,3,4-oxadiazole derivative 1, when reacted with isothiocyanates, salicylaldehyde or 1,3-dicarbonyl compounds, formed thiazole derivatives 5a,b, coumarin derivative 6 and alkenyl derivatives 7a,b resp. Compound 7b underwent cyclization to afford pyridine derivative 8. Arylhydrazono derivatives 9a,b were produced through the reaction of compound 7a with aryldiazonium chlorides. Products 9a,b underwent cyclization to produce pyridazine derivatives 10a,b. Finally, 1,3,4-oxadiazole derivative 1 was directed toward reaction with hydrazine derivatives, bromoacetophenone and ethylchloroacetate affording compounds 11a,b, 12 and 13, resp. Fused thiophene derivatives 14a,b were produced via reaction of compounds 4a,b with a mixture of malononitrile and ethylorthoformate. Antiviral activity of the synthesized products showed that 5-(4-amino-3-ethyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5a) and 5-(4-amino-3-phenyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5b) acted as the most active agents against Feline herpes virus, Feline corona virus, Herpes simplex virus-1 and Herpes simplex virus-2, whereas compound 2-(5-(2-phenylhydrazono)-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile (11b) was the most effective against Vaccinia virus, Herpes simplex virus (TK-KOS-ACVr), Coxsackie virus B4 and Vesicular stomatitis virus.

Palabras clave

  • 1,3,4-oxadiazole derivatives
  • thiophene
  • coumarin
  • thiazole
  • pyridine
  • pyridazine
  • antiviral activity
Acceso abierto

Antimicrobial assesment of aroylhydrazone derivatives in vitro

Publicado en línea: 28 Mar 2019
Páginas: 277 - 285

Resumen

Abstract

Aroylhydrazones 1–13 were screened for antimicrobial and antibiofilm activities in vitro. N′-(2-hydroxy-phenylmethylidene)-3-pyridinecarbohydrazide (2), N′-(5-chloro-2-hydroxyphenyl-methylidene)-3-pyridinecarbohydrazide (10), N′-(3,5-chloro-2-hydroxyphenylmethylidene)-3-pyridinecarbohydrazide (11), and N′-(2-hydroxy-5-nitrophenylmethylidene)-3-pyridinecarbohydrazide (12) showed antibacterial activity against Escherichia coli, with MIC values (in µmol mL−1) of 0.18–0.23, 0.11–0.20, 0.16–0.17 and 0.35–0.37, resp. Compounds 11 and 12, as well as N′-(2-hydroxy-3-methoxyphenylmethylidene)-3-pyridinecarbohydrazide (6) and N′-(2-hydroxy-5- methoxyphenylmethylidene)-3-pyridinecarbohydrazide (8) showed antibacterial activity against Staphylococcus aureus, with the lowest MIC values of 0.005–0.2, 0.05–0.12, 0.06–0.48 and 0.17–0.99 µmol mL−1. N′-(2-hydroxy-5-methoxyphenylmethylidene)-3-pyridinecarbohydrazide (7) showed antifungal activity against both fluconazole resistant and susceptible C. albicans strains with IC90 range of 0.18–0.1 µmol mL−1. Only compound 11 showed activity against C. albicans ATCC 10231 comparable to the activity of nystatin (the lowest MIC 4.0 ×10−2vs. 1.7 × 10−2 µmol mL−1). Good activity regarding multi-resistant clinical strains was observed for compound 12 against MRSA strain (MIC 0.02 µmol mL−1) and compounds 2, 6 and 12 against ESBL+ E. coli MFBF 12794, with the lowest MIC for compound 12 (IC50 0.16 µmol mL−1). Anti-biofilm activity was found for compounds 2 (MBFIC 0.015–0.02 µmol mL−1 against MRSA) and 12 (MBFIC 0.013 µmol mL−1 against EBSL+ E. coli). In the case of compound 2 against MRSA biofilm formation, MBFIC values were comparable to those of gentamicin sulphate, whereas in the case of compound 12 and EBSL+ E. coli even more favourable activity compared to gentamicin was observed.

Palabras clave

  • aroylhydrazones
  • antimicrobial
  • antibiofilm
  • MDR strains
Acceso abierto

The absorption of oral morroniside in rats: In vivo, in situ and in vitro studies

Publicado en línea: 28 Mar 2019
Páginas: 287 - 296

Resumen

Abstract

Morroniside is one of the most important iridoid glycosides from Cornus officinalis Sieb. et Zucc. In the present study, the pharmacokinetics and bioavailability studies of morroniside were conducted on Sprague-Dawley (SD) rats. A rat in situ intestinal perfusion model was used to characterize the absorption of morroniside. Caco-2 cells were used to examine the transport mechanisms of morroniside. The pharmacokinetic study of morroniside exhibited linear dose-proportional pharmacokinetic characteristics and low bioavailability (4.3 %) in SD rats. Its average Peff value for transport across the small intestinal segments changed from (3.09 ± 2.03) × 10−6 to (4.53 ± 0.94) × 10−6 cm s−1. In Caco-2 cells, the Papp values ranged from (1.61 ± 0.53) × 10−9 to (1.19 ± 0.22) × 10−7 cm s−1 for the apical to basolateral side and the Pratio values at three concentrations were all lower than 1.2. Morroniside showed poor absorption and it might not be a specific substrate of P-glycoprotein (P-gp).

Palabras clave

  • morroniside
  • pharmacokinetics
  • absorption
  • rats
  • single-pass intestinal perfusion
  • Caco-2 cell
10 Artículos
Acceso abierto

Core-shell nanofibers as drug delivery systems

Publicado en línea: 28 Mar 2019
Páginas: 131 - 153

Resumen

Abstract

Core-shell nanofibers have grown in popularity over the last decade owing to their special features and their many applications in biomedicine. They can be produced by electrospinning of immiscible polymer blends or emulsions through a single nozzle or by electrospinning using a coaxial nozzle. Several of the electrospinning parameters allow great versatility for the compositions and diameters of core-shell nanofibers to be produced. Morphology of core-shell nanofibers can be investigated using transmission electron microscopy and, in some cases, scanning electron microscopy. Several studies have shown that core-shell nanofibers have some advantages over monolithic nanofibers, such as better drug, protein, gene or probiotic incorporation into the nanofibers, greater control over drug release, and maintenance of protein structure and activity during electrospinning. We herein review the production and characterization of core-shell nanofibers, the critical parameters that affect their development, and their advantages as delivery systems.

Palabras clave

  • coaxial electrospinning
  • emulsion electrospinning
  • core-shell nanofibers
  • nanotechnology
  • nanodelivery system
  • drug release
Acceso abierto

How to assess orodispersible film quality? A review of applied methods and their modifications

Publicado en línea: 28 Mar 2019
Páginas: 155 - 176

Resumen

Abstract

In recent years, there has been a tendency toward creating innovative, easy to use and patient-friendly drug delivery systems suitable for every consumer profile, which would ensure safety, stability and acceptability of a drug. One of the relatively novel and promising approaches is the manufacture of orodispersible films (ODFs), which is an upcoming area of interest in drug delivery. They are defined as polymer thin films that disintegrate in the oral cavity within seconds, without drinking water or chewing, and eliminate the risk of choking. Gaining special usefulness in therapies of children and the elderly, ODFs seem to fill the gap in the range of preparations available for these groups of patients. As no detailed monography of ODFs including testing methods and uniform requirements has been presented in any of the pharmacopoeias to date, the aim of this article is to give an overview of the applied testing methods, their modifications and innovative approaches related to ODF quality assessment.

Palabras clave

  • orodispersible film
  • quality assessment
  • ODF testing methods
  • mechanical properties
  • disintegration time
Acceso abierto

Chemistry and pharmacological diversity of quinoxaline motifs as anticancer agents

Publicado en línea: 28 Mar 2019
Páginas: 177 - 196

Resumen

Abstract

Surpassing heart diseases, cancer is taking the lead as the deadliest disease because of its fast rate of spreading in all parts of the world. Tireless commitment to searching for novel therapeutic medicines is a worthwhile adventure in synthetic chemistry because of the drug resistance predicament and regular outbreak of new diseases due to abnormal cell growth and proliferation. Medicinal chemistry researchers and pharmacists have unveiled quinoxaline templates as precursors of importance and valuable intermediates in drug discovery because they have been established to possess diverse pharmacological potentials. Hence, this review highlights the current versatile routes to accessing functionalized quinoxaline motifs and harnessing their documented therapeutic potentials for anticancer drug development.

Palabras clave

  • quinoxaline
  • anticancer activity
  • pharmacophore
Acceso abierto

Transdermal patches: Design and current approaches to painless drug delivery

Publicado en línea: 28 Mar 2019
Páginas: 197 - 215

Resumen

Abstract

Use of transdermal patches can evade many issues associated with oral drug delivery, such as first-pass hepatic metabolism, enzymatic digestion attack, drug hydrolysis and degradation in acidic media, drug fluctuations, and gastrointestinal irritation. This article reviews various transdermal patches available in the market, types, structural components, polymer role, and the required assessment tools. Although transdermal patches have medical applications for smoking cessation, pain relief, osteoporosis, contraception, motion sickness, angina pectoris, and cardiac disorders, advances in formulation development are ongoing to make transdermal patches capable of delivering more challenging drugs. Transdermal patches can be tailored and developed according to the physicochemical properties of active and inactive components, and applicability for long-term use. Therefore, a number of chemical approaches and physical techniques for transdermal patch development are under investigation.

Palabras clave

  • transdermal patch
  • transdermal drug delivery
  • polymer matrix
  • adhesives
  • skin formulation
Acceso abierto

Quantitative analysis and resolution of pharmaceuticals in the environment using multivariate curve resolution-alternating least squares (MCR-ALS)

Publicado en línea: 28 Mar 2019
Páginas: 217 - 231

Resumen

Abstract

The study presents the application of multivariate curve resolution alternating least squares (MCR-ALS) with a correlation constraint for simultaneous resolution and quantification of ketoprofen, naproxen, paracetamol and caffeine as target analytes and triclosan as an interfering component in different water samples using UV-Vis spectrophotometric data. A multivariate regression model using the partial least squares regression (PLSR) algorithm was developed and calculated. The MCR-ALS results were compared with the PLSR obtained results. Both models were validated on external sample sets and were applied to the analysis of real water samples. Both models showed comparable and satisfactory results with the relative error of prediction of real water samples in the range of 1.70–9.75 % and 1.64–9.43 % for MCR-ALS and PLSR, resp. The obtained results show the potential of MCR-ALS with correlation constraint to be applied for the determination of different pharmaceuticals in complex environmental matrices.

Palabras clave

  • multivariate curve resolution alternating least squares
  • correlation constraint
  • partial least squares
  • multivariate calibration
  • environmental analysis
  • UV-Vis spectrophotometry
Acceso abierto

Synthesis and antiplasmodial evaluation of novel mefloquine-based fumardiamides

Publicado en línea: 28 Mar 2019
Páginas: 233 - 248

Resumen

Abstract

The paper is focused on the synthesis and screening of the antiplasmodial activity of novel fumardiamides 5–10 with the mefloquine pharmacophore and a Michael acceptor motif. Multi-step reactions leading to the title compounds included two amide bond formations. The first amide bond was achieved by the reaction of (E)-ethyl 4-chloro-4-oxobut-2-enoate (1) and N1-(2,8-bis(trifluoromethyl)quinolin-4-yl) butane-1,4-diamine (2). The obtained ester 3 was hydrolyzed and gave acid 4, which then reacted with the selected halogenanilines in the presence of HATU/DIEA and formed products 5–10. Title compounds showed marked, dose dependent activity in vitro against hepatic stages of Plasmodium berghei. IC50 values of the most active compounds 5, 7 and 9 bearing 3-fluoro, 3-chloro and 3-trifluoromethyl substituents were 3.04–4.16 µmol L−1, respectively. On the other hand, the compounds exerted only weak activity against the erythrocytic stages of two P. falciparum strains (Pf3D7 and PfDd2) in vitro, with the exception of compound 5 (IC50 = 2.9 µmol L−1).

Palabras clave

  • mefloquine
  • 2,8-bis(trifluoromethyl)quinoline
  • fumardiamide
  • halogenaniline
  • antiplasmodial activity
Acceso abierto

Stability-indicating HPLC-PDA assay for simultaneous determination of paracetamol, thiamine and pyridoxal phosphate in tablet formulations

Publicado en línea: 28 Mar 2019
Páginas: 249 - 259

Resumen

Abstract

With the increased number of multi-drug formulations, there is a need to develop new methods for simultaneous determinations of drugs. A precise, accurate and reliable liquid chromatographic method was developed for simultaneous determination of paracetamol, thiamine, and pyridoxal phosphate in pharmaceutical formulations. Separation of analytes was carried out with an Agilent Poroshell C18 column. A mixture of ammonium phosphate buffer (pH = 3.0), acetonitrile and methanol in the ratio of 86:7:7 (V/V/V) was used as the mobile phase pumped at a flow rate of 1.8 mL min−1. Detection of all three components, impurities and degradation products was performed at the selected wavelength of 270 nm. The developed method was validated in terms of linearity, specificity, precision, accuracy, LOD and LOQ as per ICH guidelines. Linearity of the developed method was found in the range 17.5–30 µg mL−1 for thiamine, 35–60 µg mL−1 for pyridoxal phosphate and 87.5–150 µg mL−1 for paracetamol. The coefficient of determination was ≥ 0.9981 for all three analytes. The proposed HPLC method was found to be simple and reliable for the routine simultaneous analysis of paracetamol, thiamine and pyridoxal phosphate in tablet formulations. Complete separation of analytes in the presence of degradation products indicated selectivity of the method.

Palabras clave

  • paracetamol
  • thiamine
  • pyridoxine phosphate
  • degradation
  • HPLC-PDA
Acceso abierto

Synthesis and evaluation of some new 1,3,4-oxadiazoles bearing thiophene, thiazole, coumarin, pyridine and pyridazine derivatives as antiviral agents

Publicado en línea: 28 Mar 2019
Páginas: 261 - 276

Resumen

Abstract

In an attempt to produce heterocyclic compounds based on 1,3,4-oxadiazole derivatives with potential antiviral activity, synthesis of compound 1 [2-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile] was performed through the reaction of cyanoacetic acid hydrazide with carbon disulfide in alcoholic potassium hydroxide. Compound 1 has an activating methylene group, so it was directed toward some specific reactions. Thus, aryldiazonium chlorides reacted with compound 1 affording hydrazono derivatives 2a-c. Also, aromatic aldehydes reacted with compound 1 to produce compounds 3a,b. Furthermore, cyclic ketones were subjected to the synthesis of fused thiophene derivatives 4a,bvia reaction with compound 1 in the presence of elemental sulfur. In addition, 1,3,4-oxadiazole derivative 1, when reacted with isothiocyanates, salicylaldehyde or 1,3-dicarbonyl compounds, formed thiazole derivatives 5a,b, coumarin derivative 6 and alkenyl derivatives 7a,b resp. Compound 7b underwent cyclization to afford pyridine derivative 8. Arylhydrazono derivatives 9a,b were produced through the reaction of compound 7a with aryldiazonium chlorides. Products 9a,b underwent cyclization to produce pyridazine derivatives 10a,b. Finally, 1,3,4-oxadiazole derivative 1 was directed toward reaction with hydrazine derivatives, bromoacetophenone and ethylchloroacetate affording compounds 11a,b, 12 and 13, resp. Fused thiophene derivatives 14a,b were produced via reaction of compounds 4a,b with a mixture of malononitrile and ethylorthoformate. Antiviral activity of the synthesized products showed that 5-(4-amino-3-ethyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5a) and 5-(4-amino-3-phenyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5b) acted as the most active agents against Feline herpes virus, Feline corona virus, Herpes simplex virus-1 and Herpes simplex virus-2, whereas compound 2-(5-(2-phenylhydrazono)-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile (11b) was the most effective against Vaccinia virus, Herpes simplex virus (TK-KOS-ACVr), Coxsackie virus B4 and Vesicular stomatitis virus.

Palabras clave

  • 1,3,4-oxadiazole derivatives
  • thiophene
  • coumarin
  • thiazole
  • pyridine
  • pyridazine
  • antiviral activity
Acceso abierto

Antimicrobial assesment of aroylhydrazone derivatives in vitro

Publicado en línea: 28 Mar 2019
Páginas: 277 - 285

Resumen

Abstract

Aroylhydrazones 1–13 were screened for antimicrobial and antibiofilm activities in vitro. N′-(2-hydroxy-phenylmethylidene)-3-pyridinecarbohydrazide (2), N′-(5-chloro-2-hydroxyphenyl-methylidene)-3-pyridinecarbohydrazide (10), N′-(3,5-chloro-2-hydroxyphenylmethylidene)-3-pyridinecarbohydrazide (11), and N′-(2-hydroxy-5-nitrophenylmethylidene)-3-pyridinecarbohydrazide (12) showed antibacterial activity against Escherichia coli, with MIC values (in µmol mL−1) of 0.18–0.23, 0.11–0.20, 0.16–0.17 and 0.35–0.37, resp. Compounds 11 and 12, as well as N′-(2-hydroxy-3-methoxyphenylmethylidene)-3-pyridinecarbohydrazide (6) and N′-(2-hydroxy-5- methoxyphenylmethylidene)-3-pyridinecarbohydrazide (8) showed antibacterial activity against Staphylococcus aureus, with the lowest MIC values of 0.005–0.2, 0.05–0.12, 0.06–0.48 and 0.17–0.99 µmol mL−1. N′-(2-hydroxy-5-methoxyphenylmethylidene)-3-pyridinecarbohydrazide (7) showed antifungal activity against both fluconazole resistant and susceptible C. albicans strains with IC90 range of 0.18–0.1 µmol mL−1. Only compound 11 showed activity against C. albicans ATCC 10231 comparable to the activity of nystatin (the lowest MIC 4.0 ×10−2vs. 1.7 × 10−2 µmol mL−1). Good activity regarding multi-resistant clinical strains was observed for compound 12 against MRSA strain (MIC 0.02 µmol mL−1) and compounds 2, 6 and 12 against ESBL+ E. coli MFBF 12794, with the lowest MIC for compound 12 (IC50 0.16 µmol mL−1). Anti-biofilm activity was found for compounds 2 (MBFIC 0.015–0.02 µmol mL−1 against MRSA) and 12 (MBFIC 0.013 µmol mL−1 against EBSL+ E. coli). In the case of compound 2 against MRSA biofilm formation, MBFIC values were comparable to those of gentamicin sulphate, whereas in the case of compound 12 and EBSL+ E. coli even more favourable activity compared to gentamicin was observed.

Palabras clave

  • aroylhydrazones
  • antimicrobial
  • antibiofilm
  • MDR strains
Acceso abierto

The absorption of oral morroniside in rats: In vivo, in situ and in vitro studies

Publicado en línea: 28 Mar 2019
Páginas: 287 - 296

Resumen

Abstract

Morroniside is one of the most important iridoid glycosides from Cornus officinalis Sieb. et Zucc. In the present study, the pharmacokinetics and bioavailability studies of morroniside were conducted on Sprague-Dawley (SD) rats. A rat in situ intestinal perfusion model was used to characterize the absorption of morroniside. Caco-2 cells were used to examine the transport mechanisms of morroniside. The pharmacokinetic study of morroniside exhibited linear dose-proportional pharmacokinetic characteristics and low bioavailability (4.3 %) in SD rats. Its average Peff value for transport across the small intestinal segments changed from (3.09 ± 2.03) × 10−6 to (4.53 ± 0.94) × 10−6 cm s−1. In Caco-2 cells, the Papp values ranged from (1.61 ± 0.53) × 10−9 to (1.19 ± 0.22) × 10−7 cm s−1 for the apical to basolateral side and the Pratio values at three concentrations were all lower than 1.2. Morroniside showed poor absorption and it might not be a specific substrate of P-glycoprotein (P-gp).

Palabras clave

  • morroniside
  • pharmacokinetics
  • absorption
  • rats
  • single-pass intestinal perfusion
  • Caco-2 cell

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