RESUMO
As part of our effort to identify potent α-amylase inhibitors, in the present study, a novel series of fluorinated thiazolidinone-pyrazole hybrid molecules were prepared by the condensation of 3-(aryl/benzyloxyaryl)-pyrazole-4-carbaldehydes with fluorinated 2,3-disubstituted thiazolidin-4-ones. The structures of the newly synthesized compounds were confirmed by infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and liquid chromatography-mass spectrometry data. All the compounds were screened for their α-amylase inhibitory and free radical scavenging activities by DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS methods. Among the tested compounds, compound 8g emerged as a promising α-amylase inhibitor with IC50 = 0.76 ± 1.23 µM, and it was found to be more potent than the standard drug acarbose (IC50 = 0.86 ± 0.81 µM). Compounds 8b and 8g showed strong free radical scavenging activity compared to the standard butylated hydroxyl anisole. The kinetic study of compound 8g revealed the reversible, classical competitive inhibition mode on the α-amylase enzyme. Molecular docking and dynamic simulations studies were performed for the most potent compound 8g, which displayed remarkable hydrogen bonding with the α-amylase protein (PDB ID: 1DHK).
Assuntos
Antioxidantes , Inibidores de Glicosídeo Hidrolases , Pirazóis , alfa-Amilases , Antioxidantes/química , Antioxidantes/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , Pirazóis/química , Pirazóis/farmacologia , Relação Estrutura-Atividade , alfa-Amilases/antagonistas & inibidoresRESUMO
BACKGROUND: Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. METHODS: Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. RESULTS: 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5-11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4-31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1-3.5). CONCLUSION: ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and 'trauma-informed' approaches to tackling longer-term impact of ACEs in India. FUNDING: Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).
Assuntos
Experiências Adversas da Infância , Maus-Tratos Infantis , Violência Doméstica , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
In the title mol-ecule, C(16)H(11)Cl(3)O, the dihedral angle between the two benzene rings is 33.2â (1)°. The crystal packing is stabilized by C-Hâ¯O hydrogen bonds.
RESUMO
In the title mol-ecule, C(12)H(15)NO(2), the oxazole ring adopts an envelope conformation. Overall, the mol-ecule is approximately planar, the dihedral angle between the mean plane through all but the methyl-ene C atom of the five-membered ring and the aromatic ring being 8.6â (1)°. A weak C-Hâ¯O inter-action contributes to the stabilization of the crystal structure.
RESUMO
Synthesis of a series of 7-arylidene-6-(2,4-dichlorophenyl)-3-aryloxymethyl/anilinomethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (3) by the condensation of 3-aryl-1-(2,4-dichloro-5-fluorophenyl)-2-bromo-propen-1-one (1) and 4-amino-5-mercapto-3-aryloxymethyl/anilinomethyl-1,2,4-triazoles (2) is described. The newly synthesized compounds were characterized by elemental analysis IR, 1H NMR and mass spectral data. These compounds were tested for their antimicrobial activities against Escherichia coli, Staphylococcus aureus (Smith), Psuedomonas aeruginosa (Gessard), Bacillus subtilis and Candida albicans. Some of the newly synthesized compounds were also screened for their anticancer activity. Among them compounds 3m, 3o, 3q showed in vitro anticancer activity.
Assuntos
Antibacterianos/síntese química , Antifúngicos/síntese química , Antineoplásicos/síntese química , Compostos Azo/síntese química , Compostos Azo/farmacologia , Flúor/química , Compostos de Sulfidrila/química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Compostos Azo/química , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: Measuring chemical stability of polyherbal formulations is very challenging due to diversity in phytochemical composition. As there are no comprehensive guidelines for stability testing of herbal products, there is a need for a sensitive tool to detect how the quality of herbal products varies with time under the influence of environmental conditions. AIMS: To validate the employability of high-performance thin layer chromatography (HPTLC) for real-time stability of Hutabhugadi Churna (HC). MATERIALS AND METHODS: The chromatograms were developed using toluene/ethyl acetate/formic acid (10:5:1) and ethyl acetate/formic acid (10:1) as a mobile phase for chloroform and ethanolic extract, respectively. The plates were scanned under 254, 366, 540 (pre-derivatization) and 540 nm (post-derivatization). Samples were analyzed immediately after preparation and after 3(rd) and 6(th) months of storage. Alteration of fingerprint profiles from the initial pattern, in terms of number of peaks, was employed as diagnostic tools. Percentage variation in composition at given period was calculated. RESULTS: HC is found to be stable at room temperature up to 1.3 months using the method of calculation of 10% degradation period employing slope and intercept values for the initial, 3(rd) and 6(th) months' deviation in number of bands. The data obtained were subjected to regression analysis in context to number of bands obtained. The curve was found to be linear with R(2) value of 0.89-0.96 supported by their tolerance range of 0.04-0.11. CONCLUSION: The proposed model is a new logic with prospects to become working method for stability assessment of polyherbal formulations under controlled conditions.
RESUMO
The acylhydrazones 3, obtained by the treatment of succinic acid dihydrazide 2 with furfural, nitrofurfuraldehydediacetate and substituted arylfurfurals, on oxidative cyclization with bromine in acetic acid yielded 1,2-bis(1,3,4-oxadiazol-2-yl)ethanes 4 which are further converted into 1,2-bis(4-amino-1,2,4-triazol-3-yl)ethanes 5 with hydrazine hydrate. The newly synthesised compounds are characterised by analytical, IR, NMR and mass spectral data. Most of the newly synthesised compounds have been found to be active against both Gram positive and Gram negative bacteria at less than 6 microg/mL concentration.
Assuntos
Antibacterianos/síntese química , Oxidiazóis/síntese química , Triazóis/síntese química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Oxidiazóis/farmacologia , Espectrofotometria Infravermelho , Triazóis/farmacologiaRESUMO
A series of 3-substituted 4-[5-(4-methoxy-2-nitrophenyl)-2-furfurylidene] amino-5-mercapto-1,2,4-triazoles (3) were synthesized. Aminomethylation of compounds 3 with formaldehyde and various secondary amines furnished Mannich bases 4 and 5. These compounds were characterized on the basis of IR, 1H-NMR, mass spectral data and elemental analysis. The newly synthesized compounds were screened for their anticancer activity against a panel of 60 cell lines derived from seven cancer types namely, lung, colon, melanoma, renal, ovarian, CNS and leukemia. Some of the compounds were slightly more potent.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Bases de Mannich/farmacologia , Triazóis/química , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/química , Humanos , Espectroscopia de Ressonância Magnética , Bases de Mannich/síntese química , Espectrometria de Massas , Espectrofotometria InfravermelhoRESUMO
A series of arylthioureas (1), aromatic aldehyde thiosemicarbazones (2) and 5-aryl-2-furfuraldehyde thiosemicarbazones (3) were condensed with 2,4-dichloro-5-fluorophenacyl bromide to yield respective arylaminothiazoles, arylidene/5-aryl-2-furfurylidene hydrazinothiazoles (4). The newly synthesized compounds were characterized by IR, 1H-NMR and mass spectral studies. These compounds were also screened for their antibacterial and anti-inflammatory activities. Two of the newly synthesized compounds showed anti-inflammatory activity comparable with that of Ibuprofen.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Tiazóis/síntese química , Tiazóis/farmacologia , Animais , Bactérias/efeitos dos fármacos , Carragenina , Dimetil Sulfóxido , Edema/induzido quimicamente , Edema/prevenção & controle , Tecido de Granulação/efeitos dos fármacos , Ibuprofeno/farmacologia , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Ratos , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
2-(5-Arylfurfurylidene/5-nitrofurfurylidene)-5-aryl-7-(2,4-dichloro-5-fluorophenyl)-5H-thiazolo[2,3-b]-pyrimidin-2(1H)-ones 5 and 6 are synthesized by a novel three component reaction of 4,6-diarylpyrimidino-2(1H)-thiones 4, monochloroacetic acid, arylfurfuraldehydes and 5-nitro-2-furfuraldenediacetate, respectively. The newly synthesized compounds are characterized by elemental analysis, IR, (1)H NMR and mass spectral studies. These compounds exhibited in vitro antitumour activity with moderate to excellent growth inhibition against a panel of 60 cell lines of leukemia, non-small cell lung cancer melanoma, ovarian cancer, prostate cancer and breast cancer.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Pirimidinonas/síntese química , Pirimidinonas/farmacologia , Tiazóis/síntese química , Tiazóis/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Pirimidinonas/química , Relação Estrutura-Atividade , Tiazóis/químicaRESUMO
A series of bis-phenoxyacetic acids 2 were prepared starting from corresponding unsubstituted/substituted 1,4-quinols 1. The fusion of bis-phenoxyacetic acids 2 with thiocarbohydrazide gave the corresponding bis-[4-amino-5-mercapto-1,2,4-triazol-3-yl-methyleneoxy]phenylenes (3) in a one pot reaction. The reaction of bis-triazoles 3 with various reagents afforded N-bridged heterocycles 4-6 in good yields. The newly synthesised compounds were screened for their anticancer activity against a panel of 60 cell lines derived from seven cancer types namely, lung, colon, melanoma, renal, ovarian, CNS and leukemia. Some of the tested compounds showed promising anticancer properties.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Tiadiazóis/síntese química , Tiadiazóis/farmacologia , Triazóis/síntese química , Triazóis/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Peso Molecular , Espectrofotometria Infravermelho , Células Tumorais CultivadasRESUMO
Synthesis of four 3-arylaminomethyl-4-amino-5-mercapto-1,2,4-triazoles starting from substituted anilines is described. These triazoles were employed in the synthesis of some N-bridged heterocycles carrying arylaminomethyl substituents. All the newly synthesized compounds were characterized by analytical, NMR and mass spectral studies. Some of the newly synthesized compounds were screened for their antibacterial and antiviral properties.
Assuntos
Anti-Infecciosos/síntese química , Antivirais/síntese química , Triazóis/síntese química , Antibacterianos , Anti-Infecciosos/farmacologia , Antivirais/farmacologia , Bactérias/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Triazóis/farmacologia , Ensaio de Placa Viral , Vírus/efeitos dos fármacosRESUMO
4-Amino-6-arylmethyl-3-mercapto-1,2,4-triazin-5(4H)-ones 1 are condensed with aromatic carboxylic acids, aryloxyacetic acids and anilinoacetic acids 2 to yield 7-substituted-3-arylmethyl-4H-1,3,4-thiadiazolo[2,3-c]-1,2,4-tr iazin-4-ones 3. Phosphorus oxychloride is used as cyclizing agent. Some of the newly synthesized compounds are screened for their antibacterial activities.
Assuntos
Antibacterianos/síntese química , Tiadiazóis/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Análise Espectral , Staphylococcus aureus/efeitos dos fármacos , Tiadiazóis/química , Tiadiazóis/farmacologiaRESUMO
A series of bis-[4-amino-5-mercapto-1,2,4-triazol-3-yl] alkanes have been synthesized and were converted into bis-[1,2,4-triazolo[3,4-b]-1,3,4-thiadiazol-4-yl] alkanes. The newly synthesized compounds were characterized by analytical IR, NMR and mass spectral studies. Some of the newly synthesized compounds were screened for their antibacterial properties and exhibited activity with MIC in the range 3-12.5 micrograms/ml.
Assuntos
Antibacterianos/química , Compostos Heterocíclicos/química , Triazóis/química , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Análise Espectral , Triazóis/farmacologiaRESUMO
Arylfurylpropenones 3 were synthesized by Claisen-Schmidt condensation of arylfurfurals 1 with various substituted acetophenones 2. Cyclocondensation of these arylfurylpropenones 3 with hydrazine hydrate and phenylhydrazine furnished 1H-pyrazolines 4 and N-phenylpyrazolines 6, respectively. In order to study the structure-activity relationships, pyrazolines 4 were converted into their N-acetyl derivatives 5. The antibacterial properties of the new pyrazoline derivatives were studied.
Assuntos
Antibacterianos/farmacologia , Chalcona/farmacologia , Furanos/farmacologia , Pirazóis/farmacologia , Antibacterianos/química , Bacillus subtilis/efeitos dos fármacos , Chalcona/síntese química , Chalcona/química , Escherichia coli/efeitos dos fármacos , Furanos/síntese química , Furanos/química , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Pirazóis/síntese química , Pirazóis/química , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
3-(3-Bromo-4-methoxyphenyl)-4-amino-5-mercapto-1,2,4-triazole was prepared starting from p-anisic acid. This new triazole was employed in the synthesis of some N-bridged heterocycles. All the newly synthesized compounds were characterized by analytical, IR, 1H-NMR and Mass Spectral studies. Some of the newly synthesized compounds were screened for their antifungal property against Thielaviopsis paradoxa, a fungus which is reported to cause stem-bleeding disease in coconut plants.
Assuntos
Antifúngicos/síntese química , Fungos Mitospóricos/efeitos dos fármacos , Tiadiazóis/síntese química , Triazóis/síntese química , Antifúngicos/farmacologia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Espectrofotometria Infravermelho , Tiadiazóis/farmacologia , Triazóis/farmacologiaRESUMO
A series of 3-substituted-4-[5-(2,4-dichlorophenyl)-2-furfurylidine]amino-5-me rcapto-1, 2,4-triazoles (3) are synthesised. Aminomethylation of 3 with formaldehyde and a primary/secondary amine furnished Mannich bases 4 and 5. Both Schiff bases 3 and Mannich bases 4 and 5 are characterised on the basis of IR, 1H NMR, mass spectral data and elemental analysis. All the newly synthesised compounds are tested for their antibacterial activities. Some of the selected compounds are also tested for their fungicidal and herbicidal properties.
Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Furaldeído/análogos & derivados , Furaldeído/química , Furanos/síntese química , Furanos/farmacologia , Bases de Mannich/química , Anti-Infecciosos/química , Furanos/química , Herbicidas/síntese química , Herbicidas/química , Herbicidas/farmacologia , Estrutura Molecular , Análise EspectralRESUMO
A series of 4-[5-(halophenyl)-2-furfurylidene)] amino-3-mercapto-5-substituted-1,2,4-triazoles (3) were synthesized. Aminomethylation of 3 with formaldehyde and a secondary amine furnished Mannich bases, 4. Both Schiff bases and Mannich bases were characterized on the basis of IR, NMR, mass spectral data and elemental analysis. All the newly synthesized compounds were tested for their antibacterial activities. Some of them carrying morpholino and N-methylpiperazino residues were found to be promising antibacterial agents.
Assuntos
Antibacterianos/síntese química , Furanos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Furanos/química , Furanos/farmacologia , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Análise Espectral , Staphylococcus aureus/efeitos dos fármacosRESUMO
4-Amino-6-phenyl/methyl-3-mercapto-1,2,4-triazin-5(4H)-ones (1) are condensed with an aromatic carboxylic acid, aryloxyacetic acid or anilinoacetic acid (2), to yield 7-substituted-3-phenyl/methyl-4H-1,3,4-thiadiazolo-[2,3-c]-1,2,4-+ ++triazin-4- ones (3). Phosphorus oxychloride is used as a cyclizing agent. All the synthesized compounds are screened for their antibacterial activities against S. aureus, E. coli, P. aeruginosa and G. bacillus.
Assuntos
Anti-Infecciosos/síntese química , Triazinas/síntese química , Anti-Infecciosos/farmacologia , Estrutura Molecular , Triazinas/farmacologiaRESUMO
A series of new furanopeptides (3) are prepared by the coupling of arylsubstituted furoic acids (1) with amino acid methyl esters, di and tetra-peptide methyl esters using dicyclohexyl carbodiimide (DCC) as coupling agent. Some of the newly synthesized compounds are characterized on the basis of IR, 1H NMR, mass spectral data and elemental analysis. Some of the selected compounds are also tested for their antibacterial properties.