RESUMEN
In this study we report the synthesis and activity against bovine viral diarrhea virus (BVDV) of a novel series of bicycle δ-sultones containing γ-lactones. BVDV is responsible for major losses in cattle. Some of the synthesized δ-sultones showed pronounced anti-BVDV activity with EC50 values of 0.12-1.0µM and no significant cytotoxicity. Among them, the ortho bromosubstituted derivative 4f (EC50=0.12µM) showed better antiviral activity than other derivatives and was 10 fold more that of than positive control ribavirin (EC50=1.3µM). BVDV is also considered to be a valuable surrogate for the hepatitis C virus (HCV) in antiviral drug studies. The above results provided a novel candidate for the development of anti-HCV agents.
Asunto(s)
Antivirales/síntesis química , Antivirales/farmacología , Virus de la Diarrea Viral Bovina/efectos de los fármacos , Hepacivirus/efectos de los fármacos , Animales , Bovinos , Modelos Animales de Enfermedad , Diseño de FármacosRESUMEN
In the present study, andrographolide (Andro, 1) derivatives were screened to identify potent inhibitors against tumor-cell migration and invasion, and associated structure-activity relationships were studied. Compared to 1, compounds 8a-8d exhibited more potent activities against migration in SGC-7901, PC-3, A549, HT-29 and Ec109 cell lines. Improved activities against tumor-cell migration and invasion were proved to be associated with the down-regulation of MMPs.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Diterpenos/química , Diterpenos/farmacología , Neoplasias/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Diterpenos/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Células HT29 , Humanos , Neoplasias/patología , Relación Estructura-ActividadRESUMEN
Andrographolide (1) is a major diterpene lactone exhibiting anti-inflammatory effects and is found in the plant Andrographis paniculata (Burm. f) Nees, which is widely used in Traditional Chinese Medicine. Synthesis of more effective drugs from andrographolide is very interesting and can prove to be highly useful. In this study, we investigated the anti-inflammatory effects of andrographolide and its derivatives (compounds 2-6) through dimethylbenzene-induced ear edema in mice. Substances under study were administrated intragastrically and the structure-activity relationship was analyzed. Results showed that compounds 5 and 6 significantly inhibited ear edema compared with compound 1 (p<0.05), indicating that the introduction of p-Chlorobenzylidene to C-15 of compound 2 enhances the anti-inflammatory effect. Moreover, compound 6 exhibited the strongest anti-inflammatory effect against ear edema in mice (79.4%; 1.35 mmol/kg, ig) and paw edema in rats (50.4%; 0.90 mmol/kg, ig). In addition, compound 6 significantly (p<0.05) inhibited granuloma formation and reduced the increase in vascular permeability induced by peritoneal injection of 0.6% acetic acid solution in mice. Findings indicate that compound 6 exerts its enhanced anti-inflammatory effects by decreasing serum iNOS activity, NO production, and PGE(2) production.
Asunto(s)
Antiinflamatorios/farmacología , Dinoprostona/biosíntesis , Diterpenos/química , Diterpenos/farmacología , Enfermedades del Oído/tratamiento farmacológico , Edema/tratamiento farmacológico , Óxido Nítrico/biosíntesis , Animales , Compuestos de Bencilideno , Enfermedades del Oído/inducido químicamente , Edema/inducido químicamente , Granuloma/tratamiento farmacológico , Masculino , Ratones , Óxido Nítrico Sintasa de Tipo II/sangre , Compuestos Policíclicos/química , Compuestos Policíclicos/farmacología , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Xilenos/toxicidadRESUMEN
A series of novel 3beta, 7alpha, 11alpha-trihydroxy-pregn-21-benzylidene-5-en-20-one derivatives were synthesized and characterized by NMR, HRMS. The pregnenolone (1) was first biotransformed by Mucor circinelloides var lusitanicus to 3beta, 7alpha, 11alpha-trihydroxy-pregn-5-en-20-one (3), then 3 was treated with various benzaldehydes to produce 3beta, 7alpha, 11alpha-trihydroxy-pregn-21-benzylidene-5-en-20-one derivatives. These derivatives showed remarkable activity against EC109 cells. The absolute configuration of 3 was also confirmed by signal-crystal X-ray analysis.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Pregnenolona/análogos & derivados , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Modelos Moleculares , Estructura Molecular , Mucor/metabolismo , Pregnenolona/síntesis química , Pregnenolona/química , Pregnenolona/farmacología , Relación Estructura-ActividadRESUMEN
By means of functional interconversions in ring D of the tetracyclic diterpene isosteviol (ent-16-ketobeyeran-19-oic acid 1), various 15- and 16-substituted isosteviol derivatives were stereoselectively prepared. The cytotoxic activities in vitro of these new isosteviol derivatives were investigated, and some of them showed noteworthy activities against B16-F10 melanoma cells.
Asunto(s)
Diterpenos de Tipo Kaurano/síntesis química , Diterpenos de Tipo Kaurano/farmacología , Animales , Línea Celular Tumoral , Química Farmacéutica/métodos , Simulación por Computador , Cristalografía por Rayos X/métodos , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Melanoma Experimental/tratamiento farmacológico , Ratones , Modelos Químicos , Estructura Molecular , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Considerable interest has been attracted in isosteviol and its derivatives because of their large variety of pharmacological activities. In this project, a series of novel compounds containing hydroxyl, hydroxymethyl group and heteroatom-containing frameworks fused with isosteviol structure were synthesized and evaluated as alpha-glucosidase inhibitors, aimed at clarifying the structure-activity correlation. The results indicated that these isosteviol derivatives were capable of inhibiting in vitro alpha-glucosidase with moderate to good activities. Among them, indole derivative 15b exhibited the highest activities and thus may be exploitable as a lead compound for the development of potent alpha-glucosidase inhibitors.
Asunto(s)
Diterpenos de Tipo Kaurano/síntesis química , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Inhibidores de Glicósido Hidrolasas , Cristalografía por Rayos X , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/farmacología , Inhibidores Enzimáticos/química , Hidroxilación , Indoles/síntesis química , Indoles/química , Indoles/farmacología , Modelos Moleculares , Estructura Molecular , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Andrographolide (1), the cytotoxic agent of the plant Andrographis paniculata, was subjected to semi-synthetic studies leading to a series of new derivatives, a novel family of glucosidase inhibitors. Nicotination of 3,19-hydroxyls in 15-alkylidene andrographolide derivatives (9) was favorable to alpha-glucosidase inhibition activity. Among them, 15-p-chlorobenzylidene-14-deoxy-11,12-didehydro-3,19-dinicotinateandrographolide (11c) was a very potent inhibitor against alpha-glucosidase with an IC50 value of 6 microM. However, all compounds concerned for beta-glucosidase showed no inhibition. All compounds synthesized were characterized by the analysis of NMR, IR, HRMS spectra and the stereochemistry of 2 was confirmed by X-ray analysis.
Asunto(s)
Diterpenos/síntesis química , Inhibidores Enzimáticos/síntesis química , Inhibidores de Glicósido Hidrolasas , Andrographis/química , Diterpenos/farmacología , Inhibidores Enzimáticos/farmacología , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Modelos Moleculares , Espectrofotometría Infrarroja , EstereoisomerismoRESUMEN
Condensation of a new unnatural sugar 1 with 1,3-dicarbonyl compounds in the presence of anhydrous zinc chloride gave the polyhydroxyalkyl-furans in excellent yields. Further modification afforded the corresponding furanosyl alpha-C-glycoside derivatives. The absolute configuration of 3-acetyl-2-methyl-5-(2'-chloro-D-galacto-tetritol-1-yl)-furan was confirmed by single-crystal X-ray analysis. The in vitro cytotoxic activities of these furanosyl C-glycosides were also investigated.
Asunto(s)
Adenocarcinoma/patología , Antineoplásicos/farmacología , Fucosa/análogos & derivados , Furanos/química , Glicósidos/farmacología , Neoplasias Pulmonares/patología , Antineoplásicos/síntesis química , Línea Celular Tumoral/efectos de los fármacos , Cloruros/química , Fucosa/química , Glicósidos/síntesis química , Humanos , Espectroscopía de Resonancia Magnética , Relación Estructura-Actividad , Compuestos de Zinc/químicaRESUMEN
N(3)-Hydroxyethyltegafur (3) was synthesized in 91.0% yield under a new condition. A series of novel fatty acid esters of 3 were synthesized. These fatty acid-nucleoside conjugates have shown cytotoxicities against Ec9706 cells and A549 cells, and the structure activity relationship was discussed.
Asunto(s)
Antimetabolitos Antineoplásicos/síntesis química , Antimetabolitos Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Ácidos Grasos/síntesis química , Ácidos Grasos/farmacología , Nucleósidos/síntesis química , Nucleósidos/farmacología , Tegafur/análogos & derivados , Tegafur/síntesis química , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Ésteres/síntesis química , Ésteres/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Espectrometría de Masa por Ionización de Electrospray , Relación Estructura-Actividad , Tegafur/farmacologíaRESUMEN
A novel and efficient method for the synthesis of quinoxaline derivatives has been developed. Isopropylidenation of 4-chloro-4-deoxy-alpha-D-galactose with 2,2-dimethoxypropane, followed by selective hydrolysis, afforded 2,3-O-isopropylidene-4-chloro-4-deoxy-D-galactose di-methyl acetal (3) as a sole product. Oxidation of compound 3 with (Bu3Sn)2O-Br2 gave corresponding hex-5-ulose derivative in high yields. The hex-5-ulose derivative reacted with o-phenylenediamines under neutral conditions to afford quinoxaline derivatives in reasonable yields. The in vitro cytotoxic activities of these quinoxaline derivatives were investigated.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Fucosa/análogos & derivados , Quinoxalinas/síntesis química , Quinoxalinas/farmacología , Carbohidratos/química , Línea Celular Tumoral , Fucosa/síntesis química , Humanos , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Espectrofotometría Infrarroja , Relación Estructura-Actividad , Sales de Tetrazolio , TiazolesRESUMEN
A series of analogues of andrographolide were synthesized and evaluated as novel alpha-glucosidase inhibitors. Among them compound 23, 15-p-methoxylbenzylidene 14-deoxy-11,12-didehydroandrographolide, was a potent inhibitor against alpha-glucosidase whose IC(50) value was 16microM. The structure-activity relationships were also discussed.
Asunto(s)
Diterpenos/química , Diterpenos/farmacología , Inhibidores Enzimáticos/farmacología , Inhibidores de Glicósido Hidrolasas , Animales , Ratas , Relación Estructura-ActividadRESUMEN
Some novel spiro-tetrahydroquinolines were stereoselectively synthesized by using keto-sugar derived from sucrose as a building block in one pot under mild conditions. The in vitro immunobiological activity and cytotoxicity of these novel tetrahydroquinolines were investigated. The results implied that these spiro-compounds have obvious bioactivity and may be structurally modified to improve bioactivity further.