RESUMEN
Efforts were taken to synthesis and characterize 2-amino-1-methyl-1H-imidazole-4(5H)-one derivatives (4a-u) through a four-step reaction. The achieved compounds in remarkable yield have characterized through standard analytical techniques such as FTIR, LC-MS, NMR, HRMS, and elemental analysis. Present study mainly aimed to evaluate 4a-u as G protein-coupled receptors (GPCR). In the mechanism, stimulation of phosphoinositide 3-kinase (PI3K) and Akt (protein kinase B) is a general reaction activated by a series of membrane-bound receptors such as GPCR. Protease-activated receptor-1 (PAR1) is a subfamily of related GPCR, which triggered by the division of fragment of its extracellular domain. Therefore, molecular docking is done to ensure the inhibition of PAR1 and PI3Kinase. PI3Kinase is a chief enzyme in the development of breast cancer via the Akt/mTOR pathway. Thus, in vitro PI3Kinase inhibition and anti-breast cancer studies has also done to screen medicinally important compounds among (4a-u). Based on the best binding affinity, in vitro relative % activity and IC50 values, compounds 4a, 4g, 4i, 4n, and 4u were screened for further preclinical studies in animal model evaluations.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Descubrimiento de Drogas , Imidazoles/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Imidazoles/síntesis química , Imidazoles/química , Ligandos , Células MCF-7 , Simulación del Acoplamiento Molecular , Estructura Molecular , Inhibidores de las Quinasa Fosfoinosítidos-3/síntesis química , Inhibidores de las Quinasa Fosfoinosítidos-3/química , Receptores Acoplados a Proteínas G/metabolismo , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
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.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Línea Celular Tumoral/efectos de los fármacos , Bases de Mannich/farmacología , Triazoles/química , Ensayos de Selección de Medicamentos Antitumorales , Furanos/química , Humanos , Espectroscopía de Resonancia Magnética , Bases de Mannich/síntesis química , Espectrometría de Masas , Espectrofotometría InfrarrojaRESUMEN
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.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Tiadiazoles/síntesis química , Tiadiazoles/farmacología , Triazoles/síntesis química , Triazoles/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Peso Molecular , Espectrofotometría Infrarroja , Células Tumorales CultivadasRESUMEN
Synthesis of four 1-aryl-3-[5-(p-nitrophenyl)-2-furyl]-2-propen-1-ones starting from substituted acetophenones and p-nitrophenylfurfuraldehyde is described. These propenones were then converted into corresponding dibromo derivatives which on dehydrobromination afforded alpha-bromopropenones rather than acetylenic ketones. Condensation of these dibromopropanones with 4-amino-5-mercapto-1,2,4-triazoles yielded a new class of nitrophenylfurfurylidene-1,2,4-triazolothiadiazines. The structures of nitrophenylfurfurylidene-1,2,4-triazolothiadiazines were established on the basis of analytical, IR, NMR and mass spectral studies. The formation of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines rather than 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazepines in the above condensation was unambiguously confirmed by X-ray crystallographic analysis of one of them. A possible mechanism is proposed to account for the formation of nitrophenylfurfurylidene-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines. Some of the newly synthesized triazolothiadiazines were screened for their antibacterial and antiviral properties.
Asunto(s)
Antiinfecciosos/síntesis química , Furanos/farmacología , Nitrocompuestos/farmacología , Nitrobencenos/farmacología , Antibacterianos , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antivirales/síntesis química , Antivirales/química , Antivirales/farmacología , Bacterias/efectos de los fármacos , Cristalografía por Rayos X , Evaluación Preclínica de Medicamentos , Furanos/síntesis química , Furanos/química , VIH-1/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Nitrocompuestos/síntesis química , Nitrocompuestos/química , Nitrobencenos/síntesis química , Nitrobencenos/química , Análisis Espectral , Tiadiazinas/síntesis química , Tiadiazinas/química , Tiadiazinas/farmacologíaRESUMEN
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.
Asunto(s)
Antibacterianos/farmacología , Chalcona/farmacología , Furanos/farmacología , Pirazoles/farmacología , Antibacterianos/química , Bacillus subtilis/efectos de los fármacos , Chalcona/síntesis química , Chalcona/química , Escherichia coli/efectos de los fármacos , Furanos/síntesis química , Furanos/química , Estructura Molecular , Pseudomonas aeruginosa/efectos de los fármacos , Pirazoles/síntesis química , Pirazoles/química , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
A series of 4-[5-(4-nitrophenyl-2-furfurylidene)]amino-5- mercapto-3-substituted-s-triazoles (3) and their Mannich bases (4) are synthesized. The structures of these compounds are established on the basis of elemental analysis, IR, NMR and mass spectral data. The newly synthesized compounds are screened for their antibacterial activities.
Asunto(s)
Antibacterianos/síntesis química , Triazoles/síntesis química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bases de Mannich , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Triazoles/farmacologíaRESUMEN
The preparation of twenty new 2-aminomethyl-4-(arylidene)amino- 6-arylmethyl-3-mercapto-1,2,4-triazin-5(4H)-ones(4) is described. The structural elucidation of all the compounds is carried out on the basis of analytical and spectral data. The newly synthesized compounds are evaluated for their antifungal activity against Candida albicans and Paecileomyces variotti.
Asunto(s)
Antifúngicos/síntesis química , Hongos/efectos de los fármacos , Triazinas/síntesis química , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Triazinas/farmacologíaRESUMEN
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.
Asunto(s)
Antibacterianos/síntesis química , Furanos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Bacillus subtilis/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Furanos/química , Furanos/farmacología , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Análisis Espectral , Staphylococcus aureus/efectos de los fármacosRESUMEN
A series of 4-[5-aryl-2-furfurylidene]amino-3-mercapto-5-substituted-1,2,4-tri azoles and 4-[5-Nitro-2-furfurylidene]amino-3-mercapto-5-substituted-1,2,4-tr iazoles have been synthesized and were converted into 1,2,4-triazolo [3,4-b]-1,3,4-thiadiazoles. These triazolothiadiazoles are also synthesized by an alternative method in better yields employing arylfuroic acids and s-triazoles in the presence of phosphorus oxychloride. The newly synthesized compounds are screened for their antibacterial properties.
Asunto(s)
Antibacterianos/síntesis química , Bacterias/efectos de los fármacos , Tiadiazoles/síntesis química , Triazoles/síntesis química , Antibacterianos/farmacología , Fenómenos Químicos , Química Física , Pruebas de Sensibilidad Microbiana , Tiadiazoles/farmacología , Triazoles/farmacologíaRESUMEN
The preparation of fifteen new 7H, 6-[5-(4-nitrophenyl)-2-furyl]-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine is described. The structural elucidation of all the compounds is carried out on the basis of analytical and spectral data. The newly synthesized compounds are evaluated for their antibacterial activity against both Gram-positive and Gram-negative bacteria.
Asunto(s)
Antibacterianos/síntesis química , Bacterias/efectos de los fármacos , Tiadiazinas/síntesis química , Triazoles/síntesis química , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Tiadiazinas/farmacología , Triazoles/farmacologíaRESUMEN
A number of arylfurylvinylquinazolinones were prepared as possible antibacterial agents. The structural elucidations of all the compounds were carried out on the basis of analytical and spectral data. The newly synthesised compounds were screened for their antibacterial properties against both Gram-positive and Gram-negative bacteria.