Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52
Filtrar
Mais filtros

País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Health Info Libr J ; 40(1): 103-108, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36722458

RESUMO

This Regular Feature is based on a PhD study assessing the level of health literacy among university students in Pakistan. A cross-sectional survey was carried out using the validated European Health Literacy Survey (HLS-EU-Q) and non-parametric tests used to analyse data with the aim of determining the influence of personal determinants on health literacy skills. The findings of the study concluded that the population had a low health literacy level with limited skills in accessing, understanding, appraising and applying information for health care. Gender, age, and native languages, all had a statistically significant influence on health literacy skills. Practical implications are presented for the role of university libraries in supporting the development of health literacy in their undergraduate student populations are presented, including the need for the provision of health information in native languages.


Assuntos
Letramento em Saúde , Humanos , Paquistão , Estudos Transversais , Prevalência , Inquéritos e Questionários , Estudantes
2.
Pak J Pharm Sci ; 35(2): 579-585, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35642415

RESUMO

2-Furoyl-1-piperazine (1) was treated with a series of alkyl/aryl sulfonyl chlorides (2a-i) under benignant conditions to obtain its N-sulfonated derivatives (3a-i). These compounds were screened for their antibacterial potential against pathogenic bacteria. The low Minimum Inhibitory Concentration (MIC) values of these molecules, in comparison of ciprofloxacin, demonstrated their high antibacterial potential. Cytotoxic activities were ascertained through their hemolytic potential and mild hemolytic profiles of these compounds proved them to be promising compounds for drug designing and development.


Assuntos
Antibacterianos , Ciprofloxacina , Antibacterianos/farmacologia , Bactérias , Ciprofloxacina/farmacologia , Testes de Sensibilidade Microbiana , Piperazina
3.
Pak J Pharm Sci ; 33(1): 41-47, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32122829

RESUMO

The current research was commenced by reaction of 1,4-benzodioxane-6-amine (1) with 4-nitrobenzenesulfonyl chloride (2) in the presence of aqueous base under dynamic pH control at 9 to yield N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-nitrobenzenesulfonamide (3) which was further reacted with a series of alkyl/aralkyl halides (4a-i) in polar aprotic solvent using catalytic amount of lithium hydride which acts as base to afford some new N-alkyl/aralkyl-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-nitrobenzenesulfonamides (5a-i). The projected structures of all the synthesized derivatives were characterized by contemporary techniques i.e., IR, 1H-NMR and EIMS. The biofilm Inhibitory action of all synthesized molecules was carried out against Escherichia coli and Bacillus subtilis. It was inferred from their results that 5f and 5e exhibited suitable inhibitory action against the biofilms of these bacterial strains. Moreover, their cytotoxicity was also checked and it was concluded that these synthesized molecules displayed docile cytotoxicity.


Assuntos
Biofilmes/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Sulfonamidas/síntese química , Sulfonamidas/farmacologia , Sulfonamidas/toxicidade , Animais , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bovinos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/química
4.
Pak J Pharm Sci ; 33(1): 149-160, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32122843

RESUMO

A series of new compounds (5a-q), derived from 5-(1-(4-nitrophenylsulfonyl) piperidin-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol (3) were proficiently synthesized to evaluate their biological activities. 1-(4-Nitrophenylsulfonyl) piperidine-4-carbohydrazide (2) was refluxed with phenylisothiocyanate to yield an adduct which was cyclized to compound 3 by reflux reaction with 10 % potassium hydroxide. The targeted compounds 5a-q, were synthesized by stirring alkyl/aralkyl halides (4a-q) and compound 3 in a polar aprotic solvent. 1H-NMR, 13C-NMR, EI-MS and IR spectral techniques were employed to confirm the structures of all the synthesized compounds. The compounds were biologically evaluated for BSA binding studies followed by anti-bacterial, anti-inflammatory and acetylcholinesterase (AChE) activities. The active sites responsible for the best AChE inhibition were identified through molecular docking studies. Compound 5e bearing 4-chlorobenzyl moiety found most active antibacterial and anti-inflammatory agent among the synthesized compounds. The whole library of synthesized compounds except compounds 5d and 5f was found highly active for AChE inhibition and recommended for in vivo studies so that their therapeutic applications may come in utilization.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Inibidores da Colinesterase/farmacologia , Simulação de Acoplamento Molecular , Albumina Sérica/metabolismo , Triazóis/farmacologia , Antibacterianos/síntese química , Anti-Inflamatórios/síntese química , Inibidores da Colinesterase/síntese química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piperidinas/química , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
5.
Pak J Pharm Sci ; 32(2): 697-702, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31081785

RESUMO

The present investigation was undertaken to evaluate the antibacterial, antifungal and hemolytic activities of organic and aqueous fractions of Fumaria indica, Dicliptera bupleuroides and Curcuma zedoaria. The methanolic extracts of the plants were dissolved in the water (distilled) separately and then partitioned with the n-hexane, CHCl3, EtOAc and n-BuOH sequentially. Antibacterial activity was checked against Escherichia coli, Pasturella multocida, Bacillus subtilis and Staphylococcus aureus by the disc diffusion method using streptomycin sulphate, a standard antibiotic, as positive control. Antifungal activity was studied against four fungi i.e. Aspergillus niger, Aspergillus flavus, Ganoderma lucidum and Alternaria alternata by the disc diffusion method using fluconazole, a standard antifungal drug, as positive control. It was revealed that aqueous fraction of F. indica showed very good antibacterial activity against P. multocida with zone of inhibition 26mm and MIC of 98µg/mL. Its CHCl3 and n-BuOH fractions also displayed good results. Its CHCl3 fraction showed good antifungal activity against G. lucidum with zone of inhibition 24mm and MIC of 115µg/mL. Other polar fractions of F. indica showed good activity against somefungal strains. The CHCl3 and EtOAc fractions of D. bupleuroides displayed good antibacterial activity against some bacterial strains. Its EtOAc fraction showed good antifungal activity only against G. lucidum. The CHCl3 fraction of C. zedoaria showed good activity against all studied bacterial strains, while its EtOAc and n-BuOH fractions displayed good results against some bacterial strains. None of the fractions of C. zedoaria displayed antifungal activity against the under test strains. All the studied fractions of three plants showed very less toxicity except n-hexane fraction of D. bupleuroides which showed 79% toxicity.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Hemolíticos/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Acanthaceae/química , Antibacterianos/química , Antifúngicos/química , Curcuma/química , Avaliação Pré-Clínica de Medicamentos , Fumaria/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Hemolíticos/química , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/química
6.
Pak J Pharm Sci ; 32(1): 61-68, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30772791

RESUMO

In the current research work, a series of new N-(alkyl/aralkyl)-N-(2,3-dihydro-1,4-benzodioxan-6-yl)-4-chlorobenzenesulfonamides has been synthesized by reacting 1,4-benzozzdioxan-6-amine (1) with 4-chlorobenzenesulfonyl chloride (2) to yield N-(2,3-dihydro-1,4-benzodioxan-6-yl)-4-chlorobenzenesulfonamide (3) which was further reacted with different alkyl/aralkyl halides (4a-n) to afford the target compounds (5a-n). Structures of the synthesized compounds were confirmed by IR, 1H-NMR, EI-MS spectral techniques and CHN analysis data. The results of enzyme inhibition showed that the molecules, N-2-phenethyl-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5j) and N-(1-butyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5d), exhibited moderate inhibitory potential against acetylcholinesterase with IC50 values 26.25±0.11 µM and 58.13±0.15 µM respectively, whereas, compounds N-benzyl-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5i) and N-(pentane-2-yl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5f) showed moderate inhibition against α-glucosidase enzyme as evident from IC50 values 74.52±0.07 and 83.52±0.08 µM respectively, relative to standards Eserine having IC50 value of 0.04±0.0001 µM for cholinesterases and Acarbose having IC50 value 38.25±0.12 µM for α-glucosidase, respectively.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/farmacologia , Sulfonamidas/síntese química , Sulfonamidas/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/enzimologia , Butirilcolinesterase/metabolismo , Diabetes Mellitus Tipo 2/enzimologia , Espectrometria de Massas , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismo
7.
Pak J Pharm Sci ; 32(3): 987-996, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31278711

RESUMO

Heterocyclic chemistry is an important field of organic chemistry due to therapeutic potential. The minor modification in the structure of poly-functional compounds has great effect on therapeutic ability. In the presented research work, substituted 1,3,4-oxadiazole derivatives, 8a-p, have been synthesized by the reaction of 1-(4-bromomethylbenzenesulfonyl)-3-methylpiperidine (7) and 5-substituted-1,3,4-oxadiazole-2-thiol (4a-p). The 5-substituted-1,3,4-oxadiazole-2-thiol were synthesized by converting carboxylic acids correspondingly into esters, hydrazides and oxadiazoles. Secondly the electrophile, 1-(4-Bromomethylbenzenesulfonyl)-3-methylpiperidine (7), was prepared by the reaction of 3-methylpiperidine with 4-bromomethylbenzenesulfonyl chloride in the presence of water and Na2CO3 under pH of 9-10. The compounds were structurally corroborated through spectroscopic data analysis of IR, EI-MS and 1H-NMR. The screening for antibacterial activity revealed the compounds to be moderate to excellent inhibitors against bacteria under study. Anti-enzymatic activity was assessed against urease enzyme and 1-{[4-({[5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl]sulfanyl}methyl)phenyl]sulfonyl}-3-methylpiperidine (8d) was the most active one.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Urease/antagonistas & inibidores , Antibacterianos/síntese química , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/síntese química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Oxidiazóis/química , Piperidinas/química , Espectrofotometria Infravermelho , Sulfonamidas/química
8.
Pak J Pharm Sci ; 31(3): 857-866, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29716866

RESUMO

In this work, a new series of 2-[4-(2-furoyl)-1-piperazinyl]-N-aryl/aralkyl acetamides has been synthesized and evaluated for their antibacterial potential. The synthesis was initiated by the reaction of different aryl/aralkyl amines (1a-u) with 2-bromoacetylbromide (2) to obtain N-aryl/aralkyl-2-bromoacetamides (3a-u). Equimolar quantities of different N-aryl/aralkyl-2-bromoacetamides (3a-u) and 2-furoyl-1-piperazine (4) was allowed to react in acetonitrile and in the presence of K2CO3, to form 2-[4-(2-furoyl)-1-piperazinyl]-N-aryl/aralkyl acetamides (5a-u). The structural elucidation was done by EI-MS, IR and 1H-NMR techniques of all the synthesized compounds. All of the synthesized molecules were active against various Gram positive and Gram negative bacterial strains. Among them 5o and 5c showed very excellent MIC values. The cytotoxicity of the molecules was also checked to find their utility as possible therapeutic agents, where 5c (0.51%) and 5g (1.32%) are found to be least toxic in the series.


Assuntos
Acetamidas/síntese química , Antibacterianos/síntese química , Piperazinas/síntese química , Acetamidas/análise , Acetamidas/farmacologia , Antibacterianos/análise , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/fisiologia , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/fisiologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Piperazinas/análise , Piperazinas/farmacologia
9.
Pak J Pharm Sci ; 31(5): 1783-1790, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30150171

RESUMO

A number of novel 5-substituted-2-((6-bromo-3,4-methylenedioxybenzyl)thio)-1,3,4-Oxadiazole derivatives (6a-l) have been synthesized to evaluate their antibacterial activity. Using aryl/aralkyl carboxylic acids (1a-l) as precursors, 5-substituted-1,3,4-Oxadiazol-2-thiols (4a-l) were yielded in good amounts. The derivatives, 4a-l, were subjected to electrophilic substitution reaction on stirring with 6-bromo-3,4-methylenedioxybenzyl chloride (5) in DMF to synthesize the required compounds. All the synthesized molecules were well characterized by IR, 1H-NMR, 13C-NMR and EIMS spectral data and evaluated for antibacterial activity against some bacterial strains of Gram-bacteria. The molecule, 6d, demonstrated the best activity among all the synthesized molecules exhibiting weak to moderate inhibition potential.


Assuntos
Antibacterianos/análise , Antibacterianos/síntese química , Oxidiazóis/análise , Oxidiazóis/síntese química , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Humanos , Testes de Sensibilidade Microbiana/métodos , Oxidiazóis/farmacologia
10.
Pak J Pharm Sci ; 31(4(Supplementary)): 1501-1510, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30058542

RESUMO

N-(Substituted)-5-(1-(4-methoxyphenylsulfonyl)piperidin-4-yl)-4H-1,2,4-triazol-3-ylthio) acetamide were synthesized by following conventional as well as microwave assisted protocol through five consecutive steps under the impact of various reaction conditions to control the reaction time and the yield of product. Starting from 4-methoxybenzenesulfonyl chloride and ethyl isonipecotate, product 3 was obtained which was converted into product 4 by treating with hydrazine hydrate. In step 3, the product 4 was refluxed with methyl isothiocyanate and KOH to yield compound 5 which was finally treated with variety of N-substituted acetamides to yield an array of different new compounds (8a-k). These synthesized compounds were evaluated for their inhibition potential against bovine carbonic anhydrase (bCA-II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Compound 8g demonstrated good activity against bCA-II, AChE and BChE with IC50 values of 8.69 ± 0.38 µM, 11.87±0.19 µM and 26.01±0.55 µM respectively. SAR studies assisted with molecular docking were carried out to explore the mode of binding of the compounds against the studied enzymes.


Assuntos
Química Farmacêutica/métodos , Inibidores da Colinesterase/síntese química , Micro-Ondas , Simulação de Acoplamento Molecular/métodos , Triazóis/síntese química , Animais , Bovinos , Inibidores da Colinesterase/farmacologia , Estrutura Secundária de Proteína , Relação Estrutura-Atividade , Triazóis/farmacologia
11.
Pak J Pharm Sci ; 31(6 (Supplementary): 2645-2654, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30587474

RESUMO

Microwave and conventional techniques were employed to synthesize a novel array of compounds 7a-g with 1,2,4-triazole and piperidine rings having great biological importance. The microwave assisted method has a better operational scope with respect to time and yield comparative to the conventional method. 1H-NMR, 13C-NMR and IR techniques were employed to justify the structure of synthesized compounds. The antioxidant, butyrylcholinesterase inhibition and urease inhibition potential of every synthesized compound was evaluated. Every member of the synthesized series was found potent against mentioned activities. Compound 7g was the most active anti-urease agent having IC50 (µM) value 16.5±0.09 even better than the thiourea with an IC50(µM) value of 24.3±0.24. The better urease inhibition potential of 7g was also elaborated and explained by docking and bovine serum albumin (BSA) binding studies.


Assuntos
Simulação por Computador , Micro-Ondas , Simulação de Acoplamento Molecular/métodos , Soroalbumina Bovina/metabolismo , Triazóis/metabolismo , Animais , Bovinos , Ligação Proteica/fisiologia , Estrutura Terciária de Proteína , Soroalbumina Bovina/síntese química , Relação Estrutura-Atividade , Triazóis/síntese química
12.
Pak J Pharm Sci ; 31(6 (Supplementary): 2697-2708, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30587482

RESUMO

The research was aimed to unravel the enzymatic potential of sequentially transformed new triazoles by chemically converting 4-methoxybenzoic acid via Fischer's esterification to 4-methoxybenzoate which underwent hydrazinolysis and the corresponding hydrazide (1) was cyclized with phenyl isothiocyanate (2) via 2-(4-methoxybenzoyl)-N-phenylhydrazinecarbothioamide (3); an intermediate to 5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazol-3-thiol (4). The electrophiles; alkyl halides 5(a-g) were further reacted with nucleophilic S-atom to attain a series of S-alkylated 5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazole-3-thiols 6(a-g). Characterization of synthesized compounds was accomplished by contemporary spectral techniques such as FT-IR, 1H-NMR, 13C-NMR and EI-MS. Excellent cholinesterase inhibitory potential was portrayed by 3-(n-heptylthio)-5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazole; 6g against AChE (IC50; 38.35±0.62µM) and BChE (IC50; 147.75±0.67µM) enzymes. Eserine (IC50; 0.04±0.01µM) was used as reference standard. Anti-proliferative activity results ascertained that derivative encompassing long straight chain substituted at S-atom of the moiety was the most potent with 4.96 % cell viability (6g) at 25µM and with 2.41% cell viability at 50µMamong library of synthesized derivatives. In silico analysis also substantiated the bioactivity statistics.


Assuntos
Inibidores da Colinesterase/síntese química , Simulação por Computador , Simulação de Acoplamento Molecular/métodos , Compostos de Sulfidrila/síntese química , Triazóis/síntese química , Inibidores da Colinesterase/metabolismo , Células HCT116 , Humanos , Compostos de Sulfidrila/metabolismo , Triazóis/metabolismo
13.
Pak J Pharm Sci ; 31(3(Supplementary)): 1051-1059, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29731443

RESUMO

An electrophile, N-(1,3-thiazol-2-yl)-2-bromoacetamide (3), was synthesized by the reaction of 1,3-thiazole-2-amine (1) and 2-bromoethanoyl bromide (2) in an aqueous medium. A series of carboxylic acids, 7a-j, were converted into 1,3,4-oxadiazole heterocyclic core, through a series of three steps. The final compounds, 8a-j, were synthesized by stirring 7a-j and 3 in an aprotic polar solvent. The structural elucidation of the synthesized compounds was supported by IR, EI-MS, 1H-NMR, and 13C-NMR spectral data. Title compounds were evaluated for enzyme inhibition against cholinesterases and α-glucosidase enzymes and their cytotoxic behavior was monitored using brine shrimp assay. The enzyme inhibitor potential of compounds was supported by molecular docking studies.


Assuntos
Acetamidas/síntese química , Acetamidas/farmacologia , Acetamidas/química , Animais , Artemia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
14.
Pak J Pharm Sci ; 31(6): 2477-2485, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30473521

RESUMO

The aim of the present research work was synthesis of some 2-furyl[(4-aralkyl)-1-piperazinyl]methanone derivatives and to ascertain their antibacterial potential. The cytotoxicity of these molecules was also checked to find out their utility as possible therapeutic agents. The synthesis was initiated by reacting furyl(-1-piperazinyl)methanone (1) in N,N-dimethylformamide (DMF) and lithium hydride with different aralkyl halides (2a-j) to afford 2-furyl[(4-aralkyl)-1-piperazinyl]methanone derivatives (3a-j). The structural confirmation of all the synthesized compounds was done by IR, EI-MS, 1H-NMR and 13C-NMR spectral techniques and through elemental analysis. The results of in vitro antibacterial activity of all the synthesized compounds were screened against Gram-negative (S. typhi, E. coli, P. aeruginosa) and Gram-positive (B. subtilis, S. aureus) bacteria and were found to be decent inhibitors. Amongst the synthesized molecules, 3e showed lowest minimum inhibitory concentration MIC = 7.52±0.µg/mL against S. Typhi, credibly due to the presence of 2-bromobenzyl group, relative to the reference standard, ciprofloxacin, having MIC = 7.45±0.58µg/mL.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Piperazinas/síntese química , Piperazinas/farmacologia , Animais , Antibacterianos/toxicidade , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Bovinos , Ciprofloxacina/farmacologia , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Hemólise/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piperazinas/toxicidade , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade
15.
Pak J Pharm Sci ; 31(2(Suppl.)): 603-609, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29625931

RESUMO

The present study describes the development and validation of a simple high performance liquid chromatographic method for the determination of a novel drug candidate, 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol. The stability-indicating capacity of the method was evaluated by subjecting the compound's solution to hydrolytic, oxidative, photolytic, transition metal- and thermal- stress. The chromatographic separation was achieved over a C18 column (Promosil, 5 µm, 4.60 × 250 mm), maintained at 25°C, using an isocratic mobile phase comprising a mixture of acetonitrile and acidified water of pH 2.67 (1:1, v/v), at a flow rate of 1.00 mL/min and detection using a fluorescent light detector (excitation at 250 nm and emission at 410 nm). The Beer's law was followed over the concentration range 2.50-50.00 µg/ml. The recovery (98.56-100.19%, SD <5%), intraday accuracy and precision (97.31-100.81%, RSD <5%), inter-day accuracy and precision (97.50-100.75%, RSD <5%) and intermediate accuracy and precision (98.10-99.91%, RSD <5%) indicated that the method was reliable, repeatable, reproducible and rugged. The resolution and selectivity factors of the compound's peak from the nearest resolving peak, particularly in case of dry heat and copper metal stress, were found to be greater than 2 and 1, respectively, which indicated specificity and selectivity. The compound was extensively decomposed in alkaline-hydrolytic, oxidative, metal- and dry heat- stress. However, the compound in acidic and neutral conditions was resistant to photolysis. The results of the present study indicate that the developed method is specific, selective, sensitive and suitable, hence, may be used for quality control, stability testing and preformulation studies.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Oxidiazóis/análise , Estabilidade de Medicamentos , Limite de Detecção , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Fluorescência
16.
Pak J Pharm Sci ; 30(2): 347-353, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28649055

RESUMO

The purpose of the research work was to examine the in vitro antioxidant activity of the different aqueous and organic fractions of Lonicera quinquelocularis Hardwicke. The methanol extract was dissolved in distilled water and fractioned with n-hexane, chloroform, ethyl acetate and n-butanol, successively. The antioxidant potential of the remaining aqueous and organic fractions was determined by using 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity, total antioxidant activity, ferric reducing antioxidant power (FRAP) assay, ferric thiocyanate assay and total phenolics method. Among these fractions ethyl acetate fraction displayed the maximum antioxidant activity with IC50 of (11.13±0.12µg/ml). It also exhibited the highest total antioxidant activity (0.595±0.00), FRAP value (128.2±4.54µg/mL) and total phenolic contents (66.89±7.73µg/g) as compared to other organic fractions. Phytochemical investigation of the above mentioned fractions showed the presence of flavanoids, phenolics, terpenoids, sugars, alkaloids, tannins, saponins and cardiac glycosides in appreciable amounts, which have major contribution towards antioxidant activity.


Assuntos
Antioxidantes/farmacologia , Lonicera/química , Compostos Fitoquímicos/análise , Extratos Vegetais/farmacologia , 1-Butanol/química , Acetatos/química , Clorofórmio/química , Hexanos/química
17.
Pak J Pharm Sci ; 30(3): 675-681, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28653909

RESUMO

A facile method has been implemented for the synthesis of different N-substituted sulfamoylacetamides by reacting 4-acetamidobenzenesulfonyl chloride (1) with different alkyl/aralkyl/aryl amines (2a-q) in basic aqueous media under controlled pH to afford -[(Substitutedsulfamoyl) phenyl]acetamides (3a-q) which were confirmed through spectral analysis like FT-IR, EIMS and 1H-NMR. Moreover, the synthesized derivatives were screened against α-Chymotrypsin. The enzyme inhibitory results revealed that most of the synthesized compounds were found to be moderate enzyme inhibitors.


Assuntos
Acetamidas/farmacologia , Quimotripsina/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Acetamidas/química , Inibidores Enzimáticos/química , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Pak J Pharm Sci ; 30(5): 1743-1751, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29084697

RESUMO

The synthetic methodology is carried out in multistep which was initiated as phase I by utilizing Fischer esterification methodology of 2-phenylacetic acid (1) to ethyl-2-phenylacetate (2). The ester was reacted with hydrazine hydrate form 2-phenylacetohydrazide (3) which underwent ring closure with carbon disulfide in alcoholic base to achieve 5-benzyl-1,3,4-oxadiazole-2-thiol (4). Phase II, involved the reaction of electrophiles with 2-bromoacetylbromide (5) with arylated/arenylated amines (6a-e) in aqueous alkaline medium under vigorous shaking to generate N-substituted-2-bromoacetamides (7a-e). Finally in phase III, the parent oxadiazole reacted with N-substituted-2-bromoacetamides and in DMF/LiH to yield 2-[(5-benzyl-1,3,4-oxadiazole-2yl)sulfanyl]-N-(arylated/arenylated) acetamides (8a-e). All the derivatives were screened for their anti-enzymatic potential against acetyl/butyrylcholinesterase and lipoxygenase and for the antibacterial activity. They were found to be weak enzyme inhibitors and also possessed weak antibacterial action with the exception of 8e, which demonstrated prominent anti-enzymatic and antibacterial activity, which may be attributed to the presence of 3,4-dimethoxyphenylacetamide moiety. The LD50 data revealed that most of the N-substituted derivatives were found to be less cytotoxic.


Assuntos
Acetamidas/síntese química , Acetamidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Acetamidas/toxicidade , Acetilcolinesterase/metabolismo , Animais , Antibacterianos/toxicidade , Artemia/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/toxicidade , Dose Letal Mediana , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
19.
Pak J Pharm Sci ; 30(1): 105-112, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28603120

RESUMO

The purpose of the present investigation was to assess the enzyme inhibition, antifungal, antibacterial and hemolytic activities of various fractions of Colebrookia oppositifolia Smith. The MeOH extract of plant was dissolved in dist. water and partitioned with n-hexane, CHCl3, EtOAc and n-BuOH sequentially. Enzyme inhibition studies were done against four enzymes i.e. α-glucosidase, butyrylcholinesterase, acetyl cholinesterase and lipoxygenase. Ethyl acetate fraction possessed very good activity against α-glucosidase (IC50 57.38±1.23µg/mL). CHCl3 fraction displayed good activity against α-glucosidase and lipoxygenase while moderate activity against butyryl cholinesterase. EtOAc fraction displayed good activity against lipoxygenase. Antifungal activity was studied against four fungi i.e. Aspergillus niger, Aspergillus flavus, Ganoderma lucidum and Alternaria alternata by the disc diffusion method using fluconazole, a standard antifungal drug, as positive control. Aqueous fraction displayed good activity against G. lucidum and A. flavus. Antibacterial activity was checked against Staphylococcus aureus, Bacillus subtilis, Pasturella multocida and Escherichia coli by the disc diffusion method using streptomycin sulphate, a standard antibiotic, as positive control. Chloroform, ethyl acetate and aqueous fraction showed good activity against E. coli. Chloroform fraction showed good activity against B. subtilis. Ethyl acetate fraction showed good activity against the P. multocida. All the studied fractions showed very less toxicity i.e. < 7%.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Inibidores Enzimáticos/farmacologia , Hemólise/efeitos dos fármacos , Lamiaceae/química , Solventes/química , Acetilcolinesterase/metabolismo , Antibacterianos/isolamento & purificação , Antibacterianos/toxicidade , Antifúngicos/isolamento & purificação , Antifúngicos/toxicidade , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/toxicidade , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Lamiaceae/toxicidade , Inibidores de Lipoxigenase/isolamento & purificação , Inibidores de Lipoxigenase/farmacologia , Fitoterapia , Plantas Medicinais
20.
Pak J Pharm Sci ; 30(5): 1715-1724, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29084694

RESUMO

Heterocyclic molecules have been frequently investigated to possess various biological activities during the last few decades. The present work elaborates the synthesis and enzymatic inhibition potentials of a series of sulfonamides. A series of 1-arylsulfonyl-4-Phenylpiperazine (3a-n) geared up by the reaction of 1-phenylpiperazine (1) and different (un)substituted alkyl/arylsulfonyl chlorides (2a-n), under defined pH control using water as a reaction medium. The synthesized molecules were characterized by 1H-NMR, 13C-NMR, IR and EI-MS spectral data. The enzyme inhibition study was carried on α-glucosidase, lipoxygenase (LOX), acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE) enzymes supported by docking simulation studies and the IC50 values rendered a few of the synthesized molecules as moderate inhibitors of these enzymes where, the compound 3e exhibited comparatively better potency against α-glucosidase enzyme. The synthesized compounds showed weak or no inhibition against LOX, AChE and BChE enzymes.


Assuntos
Desenho Assistido por Computador , Desenho de Fármacos , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , Piperazinas/síntese química , Piperazinas/farmacologia , Sulfonamidas/síntese química , Sulfonamidas/farmacologia , Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/farmacologia , Espectrometria de Massas , Conformação Proteica , Espectroscopia de Prótons por Ressonância Magnética , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA