RESUMEN
Alkaline phosphatase (ALP) is an important diagnostic indicator for a number of human diseases since abnormal level of ALP is closely related to a variety of pathological processes; hence, the development of convenient and reliable assay methods for monitoring ALP is of great significance for medical sciences as well as biological diagnostics. Herein, we report the first ratiometric fluorescent sensing system for ALP. This sensing system consists of two components: the betaine-modified and positively charged polyethylenimine (PEI) and the negatively charged pyrene derivative containing one ALP-responsive phosphate group (Py-P, an aliphatic phosphate ester). In the absence of ALP, the two-component sensing system shows the excimer's emission of Py-P, since Py-P molecules complex with the positively charged polyelectrolyte via electrostatic interactions, leading to the formation of pyrene excimers. While in the presence of ALP, the phosphate moieties are cleaved from Py-P molecules due to the enzymatic reaction, thereby destroying the electrostatic interactions; as a result, the system displays the monomer emission of Py-P. This assay system is operable in aqueous media with a very low detection limit of 0.1 U/mL. The system is capable of detecting ALP in such biological fluid as serum, and this strategy may provide a new and effective approach for designing ratiometric sensing systems for detecting other biomolecules.
Asunto(s)
Fosfatasa Alcalina/sangre , Betaína/química , Colorantes Fluorescentes/química , Polietileneimina/química , Pirenos/química , Bioensayo , Humanos , Espectrometría de Fluorescencia/métodos , Electricidad EstáticaRESUMEN
Phenyl imidazolidin-2-one was introduced as the linker for novel HDAC inhibitors. A focused library of 20 compounds was designed and synthesized, among which eight compounds showed equivalent or higher potencies against HDAC1 as compared to vorinostat. In vitro antitumor activity assays in HCT-116, PC-3 and HL-60 cancer cells revealed six compounds with potent antitumor activities, and compound 1o showed 6- to 9-fold higher potencies compared to vorinostat. In an HCT-116 nude mice xenograft model, compound 1o displayed significant antitumor activity in both continuous and intermittent dosing schedules.
Asunto(s)
Antineoplásicos/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Células HL-60 , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/química , Humanos , Ratones , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Graphene-based film attracts tremendous interest in many potential applications due to its excellent thermal, electrical, and mechanical properties. This review focused on a critical analysis of fabrication, processing methodology, the interfacial modification approach, and the applications of this novel and new class material. Strong attention was paid to the preparation strategy and interfacial modification approach to improve its mechanical and thermal properties. The overview also discussed the challenges and opportunities regarding its industrial production and the current status of the commercialization. This review showed that blade coating technology is an effective method for industrial mass-produced graphene film with controllable thickness. The synergistic effect of different interface interactions can effectively improve the mechanical properties of graphene-based film. At present, the application of graphene-based film on mobile phones has become an interesting example of the use of graphene. Looking for more application cases is of great significance for the development of graphene-based technology.