RESUMEN
In the present study, some pyrazoline derivatives were synthesized to investigate their potential antinociceptive activities. 1-[(Benzoxazole/benzimidazole-2-yl)thioacetyl]pyrazoline derivatives were obtained by reacting 3,5-diaryl-1-(2-chloroacetyl)pyrazolines with 2-marcaptobenzoxazole/benzimidazole. The chemical structures of the compounds were elucidated by IR, (1)H NMR and FAB(+)-MS spectral data and Elemental Analyses. All of the compounds (100 mg/kg) exhibited significant antinociceptive activities in both hot plate and acetic acid-induced writhing tests. Naloxone (5 mg/kg) pre-treatment reversed the antinociceptive activities suggesting the involvement of opioid system in the analgesic actions. None of the compounds impaired motor coordination of animals when assessed in the Rota-Rod model. These results support the previous papers reporting the opioid sensitive antinociceptive activities of various benzoxazole/benzimidazole-pyrazoline derivative compounds.
Asunto(s)
Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/farmacología , Dimensión del Dolor/efectos de los fármacos , Pirazoles/síntesis química , Pirazoles/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Evaluación Preclínica de Medicamentos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ratones , Estructura Molecular , Naloxona/farmacología , Dimensión del Dolor/métodos , Pirazoles/química , Espectrofotometría InfrarrojaRESUMEN
The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new thiazolylhydrazone derivatives were synthesized and evaluated for antituberculosis activity. The reaction of thiosemicarbazide with acetophenone derivatives gave 1-(1-arylethylidene)thiosemicarbazide (1). The N-(1-arylethylidene)-N'-[4-(indan-5-yl)thiazol-2-yl]hydrazone (3) derivatives were synthesized by reacting 1-(1-arylethylidene)thiosemicarbazide with 1-(5-indanyl)-2-bromoethanone (2). The chemical structure of the compounds was elucidated by elemental analyses, IR, (1)H NMR, MS-FAB(+) spectral data. Antituberculosis activities of the synthesized compounds were determined by broth microdilution assay, the Microplate Alamar Blue Assay, in BACTEC12B medium and the results were screened in vitro, using BACTEC 460 Radiometric System against Mycobacterium tuberculosis H(37)Rv (ATCC 27294) at 6.25 microg/ml and some of the tested compounds showed important inhibition ranging from 92% to 96%. The compounds were also investigated for their cytotoxic properties on normal mouse fibroblast (NIH/3T3) cell line and the results obtained here showed that all the compounds used have no significant cytotoxicity at the concentrations under 50 microg/ml.
Asunto(s)
Antituberculosos/síntesis química , Hidrazonas/síntesis química , Tiazoles/síntesis química , Animales , Antituberculosos/química , Antituberculosos/farmacología , Hidrazonas/química , Hidrazonas/farmacología , Ratones , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Células 3T3 NIH , Relación Estructura-Actividad , Tiazoles/química , Tiazoles/farmacologíaRESUMEN
The reaction of acetic or propionic acid hydrazides with various aryl/alkyl isothiocyanates gave thiosemicarbazides which furnished the 1,2,4-triazoles by alkali cyclization. The 4-aryl/alkyl-5-(1-phenoxyethyl)-3-[N-(substituted)acetamido]thio-4H-1,2,4-triazole derivatives were synthesized by reacting the triazoles with 2-chloro-N-(substituted)acetamide. The chemical structures of the compounds were elucidated by IR, (1)H-NMR, FAB(+)-MS spectral data and elemental analysis. In the pharmacological studies, anti-inflammatory activities of these compounds have been screened and significant activities were observed.
Asunto(s)
Antiinflamatorios no Esteroideos , Triazoles , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/uso terapéutico , Contraindicaciones , Edema/tratamiento farmacológico , Femenino , Masculino , Ratones , Estructura Molecular , Relación Estructura-Actividad , Triazoles/síntesis química , Triazoles/química , Triazoles/uso terapéuticoRESUMEN
The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new triazoles were synthesized and evaluated for antituberculosis activity. A series of 4-arylidenamino-4H-1,2,4-triazole-3-thiol derivatives (2a-n) were synthesized from the treatment of 4-amino-4H-1,2,4-triazoles-3-thiol (1) with the respective aldehydes and were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv (ATCC 27294), using the BACTEC 460 radiometric system and BACTEC 12B medium. Compound 2k showed an intereting activity at 6.25 microg/mL with a 87 percentage inhibition.
Asunto(s)
Antibacterianos/farmacología , Antituberculosos/farmacología , Mycobacterium tuberculosis/metabolismo , Compuestos de Sulfhidrilo/química , Triazoles/farmacología , Tuberculosis/tratamiento farmacológico , Antibacterianos/química , Química Farmacéutica/métodos , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana/métodos , Modelos Químicos , Espectrofotometría Infrarroja , Triazoles/químicaRESUMEN
The increasing clinical importance of drug-resistant fungal and bacterial pathogens has lent additional urgency to microbiological research and new antibacterial compound development. For this purpose, new tert-butyl[1-benzyl-2[(4-aryl-2-thiazolyl)hydrazono]ethyl]carbamate derivatives were synthesized and evaluated for antibacterial activity. The reaction of Boc-L-phenylalaninal with thiosemicarbazide gave the thiosemicarbazone which furnished the title compounds by reaction with phenacyl bromides. The newly synthesized compounds were screened for antibacterial activity and toxicity. While microdilution broth susceptibility assay was used for the antibacterial activity evaluation of the compounds against the strains E. coli (NRRL B-3704), M. luteus (NRRL B-4375), B. cereus (NRRL B-3711), P. aeruginosa (NRRL B-23), and S. fecalis (NRRL B-14617), the Artemia salina 96-well assay was used to determine cytotoxicities of the compounds. Observations obtained from the bioassays showed that some of the compounds are highly active against E. coli, M. luteus, and B. cereus when compared with the control agent and showed low toxicity.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/toxicidad , Carbamatos/síntesis química , Carbamatos/toxicidad , Hidrazonas/síntesis química , Hidrazonas/toxicidad , Tiazoles/síntesis química , Tiazoles/toxicidad , Animales , Antibacterianos/química , Artemia/efectos de los fármacos , Bacillus cereus/efectos de los fármacos , Carbamatos/química , Enterococcus faecalis/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Hidrazonas/química , Dosificación Letal Mediana , Pruebas de Sensibilidad Microbiana/métodos , Tiazoles/químicaRESUMEN
The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new alkylsulfanyltriazoles were synthesized and evaluated for antituberculosis activity. The reaction of thienyl-2-acetic acid with thiocarbohydrazide gave the mercaptotriazoles (II). The 4-amino-5-(2-thienylmethyl)-3-[1-(2-thienyl)-3-aryl) propion-3-yl] sulfanyl-4H-1,2,4-triazole (III) derivatives were synthesized by reacting the mercaptotriazoles with chalcones (I). Antituberculosis activities of the synthesized compounds were determined by broth microdilution assay, the Microplate Alamar Blue Assay, in BACTEC 12B medium and results were screened in-vitro, using BACTEC 460 Radiometric System against Mycobacterium tuberculosis H37Rv (ATCC 27294) at 6.25 microg/ml and the tested compounds showed considerable inhibition ranging from 58-84%.
Asunto(s)
Antituberculosos/farmacología , Triazoles/farmacología , Antibacterianos/farmacología , Chalconas/química , Medios de Cultivo/farmacología , Pruebas de Sensibilidad Microbiana , Modelos Químicos , Mycobacterium tuberculosis/metabolismo , Oxazinas/farmacología , Temperatura , Tiazoles/síntesis química , Tiazoles/química , Triazoles/síntesis química , Xantenos/farmacologíaRESUMEN
The increasing clinical importance of drug-resistant fungal and bacterial pathogens has lent additional urgency to microbiological research and new antimicrobial compound development. For this purpose, new thiazole derivatives of triazoles were synthesized and evaluated for antifungal and antibacterial activity. The reaction of propionic acid hydrazides with various aryl/alkyl isothiocyanates gave thiosemicarbazides which furnished the mercaptotriazoles by alkali cyclization. The 4-phenyl/cyclohexyl-5-(1-phenoxyethyl)-3-[N-(2-thiazolyl)acetamido]thio-4H-1,2,4-triazole derivatives were synthesized by reacting the mercaptotriazoles with 2-chloro-N-(2-thiazolyl)acetamide. The chemical structures of the compounds were elucidated by IR, 1H-NMR, FAB+-MS spectral data. Their antimicrobial activities against Candida albicans (two strains), Candida glabrata, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa were investigated. The results showed that some of the compounds have very strong antifungal activity.
Asunto(s)
Antiinfecciosos/síntesis química , Tiazoles/síntesis química , Tiazoles/farmacología , Triazoles/síntesis química , Triazoles/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Candida/efectos de los fármacos , Candida/crecimiento & desarrollo , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Infrarroja , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Tiazoles/química , Triazoles/químicaRESUMEN
Chromatographic parameters (deltaR(f)), defined as a difference in the migration of tested compound on the control and peptide impregnated silica gel TLC plates, were determined for 42 arylpiperazine derivatives. An amino acid sequence of the peptide used for impregnation was derived from the III transmembrane segment of the 5-HT(1A) receptor in the close vicinity of aspartic acid (Asp 166) residue. It was found that the deltaR(f) values obtained in a model employing tetrapeptide P4LA (ADVL), as well as the calculated logP correlate with 5-HT(1A) receptor affinity of the studied compounds.