RESUMEN
In the present investigation, a series of dihydrotriazine derivatives-bearing 5-aryloxypyrazole moieties were synthesized and their structures were confirmed by different spectral tools. The biological evaluation in vitro revealed that some of the target compounds exerted good antibacterial and antifungal activity in comparison with the reference drugs. Among these novel hybrids, compound 10d showed the most potent activity with minimum inhibitory concentration values (MIC) of 0.5 µg/mL against S. aureus 4220, MRSA 3506 and E. coli 1924 strain. The cytotoxic activity of the compounds 6d, 6m, 10d and 10g was assessed in MCF-7 and HeLa cells. Growth kinetics study showed significant inhibition of bacterial growth when treated with different conc. of 10d. In vitro enzyme study implied that compound 10d exerted its antibacterial activity through DHFR inhibition. Moreover, significant inhibition of biofilm formation was observed in bacterial cells treated with MIC conc. of 10d as visualized by SEM micrographs. Twenty-nine target compounds were designed, synthesized and evaluated in terms of their antibacterial and antifungal activities.
Asunto(s)
Antibacterianos , Triazinas , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Supervivencia Celular/efectos de los fármacos , Células HeLa , Humanos , Células MCF-7 , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Tetrahidrofolato Deshidrogenasa/química , Triazinas/síntesis química , Triazinas/química , Triazinas/farmacologíaRESUMEN
In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3-a] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone. Compound 6c was the most potent agent, with an increased stroke volume of 12.53% ± 0.30% (milrinone: 2.46% ± 0.07%) at 3 × 10-5 M. The chronotropic effects of compounds having considerable inotropic effects were also evaluated.
Asunto(s)
Cardiotónicos/síntesis química , Cardiotónicos/farmacología , Piperazinas/química , Quinoxalinas/síntesis química , Quinoxalinas/farmacología , Animales , Relación Dosis-Respuesta a Droga , Atrios Cardíacos/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Milrinona/farmacología , Estructura Molecular , Contracción Miocárdica/efectos de los fármacos , Conejos , Volumen Sistólico/efectos de los fármacosRESUMEN
A series of dehydroepiandrosterone derivatives containing an acid ester was synthesized and evaluated for their antitumor activity on ES-2, A549, and HepG2 cells by the MTT assay. Most compounds showed antitumor activity, while compounds 1c, 2i, and 2o exhibited more potential inhibitory effects compared with dehydroepiandrosterone on ES-2 cells, A549 cells, and HepG2 cells, respectively.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Deshidroepiandrosterona/análogos & derivados , Deshidroepiandrosterona/farmacología , Antineoplásicos/síntesis química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Deshidroepiandrosterona/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Neoplasias/tratamiento farmacológicoRESUMEN
A series of chalcone derivatives bearing the 2,4-thiazolidinedione and benzoic acid moieties (8a-s) were synthesized, characterized, and evaluated for their anti-bacterial activity. Among the tested compounds, the most effective were 8a, 8h, 8k, 8n and 8q with MIC value in the range of 0.5-4 µg/mL against six Gram-positive bacteria (including multidrug-resistant clinical isolates). None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 and E. coli 1682 at 64 µg/mL.
Asunto(s)
Antibacterianos/síntesis química , Ácido Benzoico/química , Proliferación Celular/efectos de los fármacos , Chalcona/síntesis química , Staphylococcus aureus/efectos de los fármacos , Tiazolidinedionas/química , Antibacterianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Chalcona/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/crecimiento & desarrolloRESUMEN
A series of panaxadiol derivatives have been synthesized by the simple acylation of the 3-hydroxy group of panaxadiol. The anti-tumor activities of the synthesized compounds were evaluated against a panel of human tumor cell lines by the standard MTT assay. Compounds 2, 11, 12, 13, 14, 15 and 16 showed stronger antiproliferative activities than that of Rg3 and PD on the growth of the distinct cancer cell lines in vitro.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Ginsenósidos/química , Ginsenósidos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Ginsenósidos/síntesis química , Humanos , Conformación Molecular , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
In an attempt to search for more potent positive inotropic agents, a series of N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(substitutedbenzyl-[1,4]diazepan-1-yl)acetamides were synthesized and evaluated for positive inotropic activity by measuring left atrium stroke volume in isolated rabbit heart preparations. Some of these derivatives exhibited favorable activity compared with the standard drug, milrinone, among which 2-(4-(4-methylbenzyl)-[1,4]-diazepan-1-yl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide (6m) was the most potent, increasing stroke volume by 8.38±0.16% (milrinone 2.45± 0.06%) at 3 x 10(-5) m. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.
Asunto(s)
Acetamidas , Azepinas/síntesis química , Azepinas/farmacología , Cardiotónicos , Corazón/efectos de los fármacos , Milrinona/farmacología , Contracción Miocárdica/efectos de los fármacos , Volumen Sistólico/efectos de los fármacos , Triazoles/síntesis química , Triazoles/farmacología , Acetamidas/síntesis química , Acetamidas/farmacología , Animales , Cardiotónicos/síntesis química , Cardiotónicos/farmacología , Técnicas de Cultivo de Órganos/métodos , ConejosRESUMEN
We describe the synthesis and positive inotropic evaluation of a series of 2-(4-substitutedbenzyl-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-phenyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides by measuring left atrial stroke volume in preparations of isolated rabbit-heart. Several compounds were developed from, and showed favorable activities compared with the standard drug milrinone. Compound 5o was the most potent with an increased stroke volume of 9.17 ± 0.14% (milrinone 2.47 ± 0.08%) at 3 × 10â»5 M in our in-vitro study. The chronotropic effects of those compounds having inotropic effects were also evaluated.
Asunto(s)
Acetamidas/síntesis química , Cardiotónicos/síntesis química , Corazón/efectos de los fármacos , Quinolinas/síntesis química , Volumen Sistólico/efectos de los fármacos , Acetamidas/farmacología , Animales , Frecuencia Cardíaca , Técnicas In Vitro , Quinolinas/farmacología , Conejos , Relación Estructura-ActividadRESUMEN
In an attempt to search for more potent positive inotropic agents, a series of 2-(4-substitutedmethylpiperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamides were synthesized and their positive inotropic activities were evaluated by measuring left atrium stroke volume on isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone, among which 2-(4-(4-methylbenzyl)piperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamide 4e showed the most potent activity with the 5.09+/-0.00% increased stroke volume (milrinone 1.67+/-0.64%) at a concentration of 1x10(-5)M in our in vitro study. The chronotropic effects of those compounds having significant inotropic effects were also evaluated in this work.
Asunto(s)
Acetamidas/síntesis química , Acetamidas/farmacología , Cardiotónicos/síntesis química , Cardiotónicos/farmacología , Acetamidas/química , Animales , Función del Atrio Izquierdo/efectos de los fármacos , Cardiotónicos/química , Atrios Cardíacos/efectos de los fármacos , Oxazinas/química , Quinolonas/química , Conejos , Estándares de Referencia , Análisis Espectral , Volumen Sistólico/efectos de los fármacosRESUMEN
In an attempt to search for more potent positive inotropic agents, a series of 2-(4-(4-substituted benzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides was synthesized and their positive inotropic activities were evaluated by measuring left atrium stroke volume on isolated rabbit-heart preparations. Several compounds showed favorable activity compared with the standard drug Milrinone among which 2-(4-(4-(2-chlorobenzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide 6e was found to have the most desirable potency with the 6.79 +/- 0.18% increased stroke volume (Milrinone: 1.67 +/- 0.64%) at a concentration of 1 x 10(-5) M in our in-vitro study. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.