RESUMEN
A series of novel 11H-benzo[a]carbazole-5-carboxamide derivatives were designed, synthesized and evaluated for their antitumor activity against human cancer A549 and HCT-116 cell lines. Most of the compounds showed potent antitumor activities, and compound 8 displayed remarkable in vitro and in vivo anticancer activity comparable to that of amonafide.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/uso terapéutico , Carbazoles/química , Carbazoles/uso terapéutico , Amidas/síntesis química , Amidas/química , Amidas/farmacología , Amidas/uso terapéutico , Animales , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Carbazoles/síntesis química , Carbazoles/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Ratones Desnudos , Neoplasias/tratamiento farmacológico , Relación Estructura-ActividadRESUMEN
PTD4-apoptin protein enters cells and harbors tumor-selective cell death activity. Dacarbazine is the mainstay of treatment for malignant melanoma. In this study, we investigated the cytotoxic effect of PTD4-apoptin protein and/or dacarbazine in mouse B16-F1 and human A875 and SK-MEL-5 melanoma cells in vitro and by means of a mouse B16-F1 melanoma model in vivo. PTD4-apoptin protein inhibits the growth of B16-F1, A875 and SK-MEL-5 melanoma cells in a dose-dependent manner, but not in normal human cell lines WI-38 and L-02. PTD4-apoptin combined with dacarbazine revealed a synergistic cytotoxic effect (coefficient of drug interaction<1) in all three different tumor cell lines. In vivo, PTD4-apoptin protein and dacarbazine alone effectively inhibited the growth of B16-F1 melanoma in C57BL/6 mice. Strikingly, combined PTD4-apoptin/dacarbazine treatment significantly increased the antitumor effect in comparison to the single treatments. As important, a combined PTD4-apoptin/dacarbazine treatment with a 50% reduction of dacarbazine revealed similar antitumor activities, without detectable hematologic side effects. A combined PTD4-apoptin/dacarbazine treatment represents a promising novel efficient and safe anticancer strategy.
Asunto(s)
Proteínas de la Cápside/farmacología , Dacarbazina/farmacología , Melanoma/tratamiento farmacológico , Proteínas Recombinantes de Fusión/química , Animales , Antineoplásicos Alquilantes/farmacología , Proteínas de la Cápside/administración & dosificación , Proteínas de la Cápside/química , Línea Celular , Línea Celular Tumoral , Sinergismo Farmacológico , Femenino , Humanos , Melanoma/patología , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BLRESUMEN
A series of R and S enantiomers of 7-(3-methylpiperazin-1-yl) quinolone derivatives were synthesized from (R)- and (S)-tert-butyl 2-methylpiperazine-1-carboxylate and tested for their antibacterial activities on 14 kinds of bacteria. Although no distinct difference in in vitro antibacterial activities was observed, 2-64-fold difference between R and S enantiomers was observed in approximately 52% of cases.
Asunto(s)
Piperazinas/química , Quinolonas/síntesis química , Estructura Molecular , Piperazinas/síntesis química , EstereoisomerismoRESUMEN
Two new 18(13-->12)-abeo-lanostane triterpenoid acids, ananosic acids B (1) and C (2), were isolated from the stems of Kadsura anaosma. Their structures were elucidated by spectral studies and chemical transformation. Compounds 1 and 2 were evaluated for cytotoxicity using CCRF-CEM leukemia cells and HeLa cells.
