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1.
Bioorg Chem ; 99: 103584, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32229345

RESUMO

Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F.


Assuntos
Anticonvulsivantes/uso terapêutico , Simulação de Acoplamento Molecular , Piridazinas/uso terapêutico , Convulsões/tratamento farmacológico , Tiazóis/uso terapêutico , Animais , Anticonvulsivantes/síntese química , Anticonvulsivantes/química , Relação Dose-Resposta a Droga , Eletrochoque , Feminino , Injeções Subcutâneas , Masculino , Camundongos , Estrutura Molecular , Pentilenotetrazol/administração & dosagem , Piridazinas/síntese química , Piridazinas/química , Convulsões/induzido quimicamente , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/química
2.
J Enzyme Inhib Med Chem ; 28(3): 552-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22380781

RESUMO

Some new 7-substituted-phenyl-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine/one/thione derivatives were synthesized by a sequence of reactions starting from appropriate aryl hydrocarbons. The final compounds were screened for antihypertensive activities by non-invasive method using Tail Cuff method. All the test compounds showed significant antihypertensive activity; 7-(biphenyl-4-yl)-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine (4p) exhibited antihypertensive activity more than the reference standard drugs.


Assuntos
Anti-Hipertensivos/síntese química , Anti-Hipertensivos/farmacologia , Piridazinas/química , Animais , Anti-Hipertensivos/química , Técnicas de Química Sintética , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Iminas/química , Piridazinas/farmacologia , Ratos , Tionas/química , Triazinas/química , Triazinas/farmacologia
3.
Acta Pol Pharm ; 70(3): 443-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23757935

RESUMO

A series of bis-chalcones (3a-g) and their flavones derivatives (4a-g) were synthesized and evaluated for their antimicrobial activity. Bis-chalcones were prepared by condensing 1,1'-(4,6-dihydroxy-1,3-phenylene)diethanone (2) with appropriate aryl aldehydes following Claisen-Schmidt reaction conditions. Oxidative cyclization of bis-chalcones (3a-g) in DMSO in the presence of iodine furnished flavones (4a-g). The synthesized compounds were evaluated for their antibacterial and antifungal actions against some selected microbes. The results of antimicrobial evaluation showed that some of the synthesized compounds were good in their antibacterial and antifungal actions.


Assuntos
Anti-Infecciosos/síntese química , Chalconas/síntese química , Flavonas/síntese química , Anti-Infecciosos/farmacologia , Chalconas/farmacologia , Flavonas/farmacologia , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
4.
Bioorg Med Chem Lett ; 22(17): 5438-44, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22840417

RESUMO

Two new series of benzimidazole bearing oxadiazole[1-(1H-benzo[d]imidazol-2-yl)-3-(5-substituted-1,3,4-oxadiazol-2-yl)propan-1-ones (4a-l)] and triazolo-thiadiazoles[1-(1H-benzo[d]imidazol-2-yl)-3-(6-(substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)propan-1-one (7a-e)] have been synthesized successfully from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (3) with an aim to produce promising anticancer agents. In vitro anticancer activities of synthesized compounds were screened at the National Cancer Institute (NCI), USA, according to their applied protocol against full NCI 60 human cell lines panel; results showed good to remarkable anticancer activity. Among them, compound (4j, NCS: 761980) exhibited significant growth inhibition and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 µM) with GI(50) values ranging from 0.49 to 48.0 µM and found superior for the non-small cell lung cancer cell lines like HOP-92 (GI(50) 0.49, TGI 19.9,LC(50) >100 and Log(10)GI(50) -6.30, Log(10)TGI -4.70, Log(10)LC(50) >-4.00).


Assuntos
Antineoplásicos/química , Benzimidazóis/química , Oxidiazóis/química , Tiadiazóis/química , Triazóis/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias/tratamento farmacológico , Oxidiazóis/síntese química , Oxidiazóis/farmacologia , Tiadiazóis/síntese química , Tiadiazóis/farmacologia , Triazóis/síntese química , Triazóis/farmacologia
5.
Bioorg Med Chem Lett ; 21(3): 1023-6, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-21211966

RESUMO

A number of 6-(substituted phenyl)-2-(4-substituted phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydropyridazin-3(2H)-one derivatives were designed and synthesized by a sequence of reactions starting from respective aryl hydrocarbons. The final compounds (4a-4u) were evaluated for antihypertensive activities by non-invasive method using Tail Cuff method. The compounds 4e, 4i and 4k showed appreciable antihypertensive activity comparable with that of standard hydralazine and propranolol.


Assuntos
Anti-Hipertensivos/síntese química , Piridazinas/química , Piridazinas/síntese química , Triazóis/síntese química , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Desenho de Fármacos , Piridazinas/farmacologia , Ratos , Triazóis/química , Triazóis/farmacologia
6.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 9): o2294-5, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22065726

RESUMO

In the title compound, C(24)H(18)O(3), the dihedral angles between the mean planes of the five-membered furan ring and the meth-oxy-substituted benzene and the adjacent and outer biphenyl benzene rings are 2.43 (7), 4.48 (7) and 30.47 (8)°, respectively. The crystal packing is stabilized by weak C-H⋯O and C-H⋯π inter-molecular hydrogen bonds and π-π stacking inter-actions [centroid-centroid distances = 3.8752 (8) and 3.8331 (8) Å].

7.
Eur J Med Chem ; 83: 630-45, 2014 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-25010935

RESUMO

Design and synthesis of new pyrimidine derivatives clubbed with thiazolidin-4-one from 4-(2-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidin-2-amine and their in vitro anticancer activities were screened at National Cancer Institute (NCI), USA against full NCI 60 cell lines. Compound 2 (NSC: 765735) exhibited remarkable growth inhibition at single dose (10 µM) and encourage chosen for broadcast at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 µM). The compound 2 was found better quality for Lung cancer cell line (HOP-92) by viewing growth inhibition (GI50 0.52) and no cytotoxicity seen (LC50 > 100). Molecular docking study was performed using Maestro 9.0 (Schrodinger Inc. USA) to provide binding mode into binding sites of CDK2. Compound 2 could be used as a lead compound for developing new potential anticancer agents.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Desenho de Fármacos , Tiazolidinas/síntese química , Tiazolidinas/farmacologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Técnicas de Química Sintética , Quinase 2 Dependente de Ciclina/química , Quinase 2 Dependente de Ciclina/metabolismo , Humanos , Simulação de Acoplamento Molecular , Conformação Proteica , Relação Estrutura-Atividade , Tiazolidinas/química , Tiazolidinas/metabolismo
8.
Acta Pharm ; 63(3): 385-96, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24152898

RESUMO

During the manufacture of bulk drug midazolam various impurities arised that can be the related products or degradation products. Structures of eight impurities that can arise during the manufacture of bulk drug midazolam were proposed. In the present work, synthesis of these impurities and their characterization by different spectroscopic techniques have been done. HPLC method was developed for the separation of impurities from the bulk drug. The developed method separates midazolam from its eight impurities/degradation products within a run time of 45 min.


Assuntos
Química Farmacêutica/métodos , Contaminação de Medicamentos , Midazolam/análise , Midazolam/síntese química , Cromatografia Líquida de Alta Pressão/métodos
9.
Eur J Med Chem ; 62: 785-98, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23333063

RESUMO

Two series of Benzimidazole clubbed with triazolo-thiadiazoles (5a-q, 5r, 5s and 5x-a(1)) and triazolo-thiadiazines (5t-w) were synthesized with an aim to produce promising anticancer agents. In vitro anticancer activities of synthesized compounds were investigated at the National Cancer Institute (NCI) against NCI 60 cell line panel; results showed good to remarkable broad-spectrum anticancer activity. Among them, the compound 5h (NCS: 760452, 1-(1H-benzo [d] imidazol-2-yl)-3-(6-(2,4-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl) propan-1-one) exhibited significant growth inhibition with GI50 values ranging from 0.20 to 2.58 µM and found superior selectivity for the leukemia cell lines and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 µM). The 5h may possibly be used as lead compound for developing new anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/química , Tiadiazinas/química , Tiadiazóis/química , Triazóis/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
10.
Drug Test Anal ; 5(8): 607-13, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23653249

RESUMO

Traditional herbal medicines (THMs) are gaining popularity worldwide as an alternative approach to prescription drugs for many reasons including a general perception that they are safe. But recently there have been number of reported studies that reveal adulteration of THMs with undeclared synthetic drugs, which may potentially cause serious toxic adverse effects. This paper reviews the various classes of synthetic drugs that were found to be adulterated in THMs worldwide. The main focus is to highlight newer analytical tools used to detect adulteration. Due to the advancement in hyphenated techniques like liquid chromatography tandem mass spectrometry (LC-MS/MS), gas chromatography-tandem mass spectrometry (GC-MS/MS) and other conventional tools, it has become possible to detect synthetic drugs and their structural analogues as adulterants even if they are present in small quantities. This review also gives an overview of health-related risks after consuming such spurious products and challenges for future perspectives to control such type of malpractices.


Assuntos
Cromatografia Líquida/métodos , Contaminação de Medicamentos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Preparações Farmacêuticas/análise , Plantas Medicinais/química , Humanos
11.
J Pharm Anal ; 3(5): 341-348, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29403837

RESUMO

Liquid chromatography tandem mass chromatography (LC-MS/MS) is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC-MS/MS has been used for pharmacokinetic studies, metabolites identification in the plasma and urine. This manuscript gives comprehensive analytical review, focusing on chromatographic separation approaches (column packing materials, column length and mobile phase) as well as different acquisition modes (SIM, MRM) for quantitative analysis of glucocorticoids and stimulants. This review is not meant to be exhaustive but rather to provide a general overview for detection and confirmation of target drugs using LC-MS/MS and thus useful in the doping analysis, toxicological studies as well as in pharmaceutical analysis.

12.
Eur J Med Chem ; 54: 855-66, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22608854

RESUMO

Starting from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (1), twenty new 1-(1H-benzo[d]imidazol-2-yl)-3-(1,3,4-oxadiazol-5-substituted derivatives-2-yl)propan-1-ones (1b-A(7)(-)(26)) were synthesized under microwave irradiation in good yields. Further, compound 1b-A(7) was reacted with different secondary amines under microwave irradiation to produce five novel 1-(1H-benzo[d]imidazol-2-yl)-3-(5-(methyl substituted)-1,3,4-oxadiazol-2-yl)propan-1-ones (1b-A(7a)(-)(e)). The title compounds were screened for their in vitro anticancer activity at National Cancer Institute (NCI), USA; at a single dose (10 µM) in NCI 60 cell line panel and results showed significant to good anticancer activity. One compound, 1b-A(18) (NSC: 759205), 1-(1H-benzo[d]imidazol-2-yl)-3-(5-(2,4-dichlorophenyl)-1,3,4-oxadiazol-2-yl)propan-1-one, emerged as lead compound; it was selected for five-dose level screening and found to have significant growth inhibition activity.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Oxidiazóis/química , Antineoplásicos/química , Benzimidazóis/química , Linhagem Celular Tumoral , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Humanos
13.
Eur J Med Chem ; 45(6): 2283-90, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20189270

RESUMO

Some 6-(substituted-phenyl)-2-(substitutedmethyl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized by reacting 6-substituted-phenyl-4,5-dihydropyridazin-3(2H)-one with cyclic secondary amine under Mannich reaction conditions. The final compounds (15-70) were evaluated for antihypertensive activities by non-invasive method using Tail Cuff method. The compounds 16, 19, 24, 30, 39, 42 and 45 showed good antihypertensive activity.


Assuntos
Anti-Hipertensivos/síntese química , Anti-Hipertensivos/farmacologia , Piridazinas/síntese química , Piridazinas/farmacologia , Animais , Anti-Hipertensivos/química , Pressão Sanguínea/efeitos dos fármacos , Piridazinas/química , Ratos
14.
J Pharm Bioallied Sci ; 2(2): 109-12, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21814442

RESUMO

BACKGROUND: Pain is an unpleasant and subjective sensation that results from a harmful sensorial stimulation, which alerts the body about current or potential damage to its tissues and organs. Fever is a complex physiological response triggered by infections or aseptic stimuli. Elevation in body temperature occurs when the concentration of prostaglandin E(2) (PGE(2)) increases within parts of the brain. Triazole derivatives have been found to possess various pharmacological and biological activities, such as, anti-inflammatory, analgesics, antipyretic, and antifungal. MATERIALS AND METHODS: Various 4-[{1-(aryl)methylidene}-amino]-3-(4-pyridyl)-5-mercapto-4H-1,2,4-triazole derivatives were synthesized by a sequence of reactions starting from isonicotinic acid hydrazide. The synthesized compounds were screened for in-vivo analgesic by the tail-flick method and anti-pyretic activities at a dose of 25 and 100 mg/kg body weight respectively. The antipyretic activity was evaluated using Brewer's yeast induced pyrexia in rats. Fever was induced by subcutaneously injecting 20 ml/kg of 20% aqueous suspension of Brewer's yeast in normal saline. RESULTS AND DISCUSSION: The analgesic screening results revealed that the compounds 3b, 3c, and 3d exhibited excellent analgesic activity at 60 and 90 minutes compared to the standard drug (Analgin). Results revealed that the compounds 3a, 3e, and 3f significantly decreased the temperature of pyretic (P<0.001) rats at one, three and six hours after compound administration as compared to Aspirin (standard drug). CONCLUSION: Compounds 3b, 3c, and 3d exhibited significant analgesic activity comparable with the standard drug analgin, using the tail flick model. Compounds 3a, 3e, and 3f showed significant anti-pyretic activities comparable with the standard drug aspirin using the yeast-induced pyrexia model.

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