RESUMEN
The overexpression of P-glycoprotein plays an important role in the process of multidrug resistance (MDR). P-gp inhibitors are one of the effective strategies to reverse tumor MDR. Novel P-gp inhibitors with phthalazinone scaffolds were designed, synthesized and evaluated. Compound 26 was found to be the most promising for further study. Compound 26 possessed high potency (EC50â¯=â¯46.2⯱â¯3.5â¯nM) and low cytotoxicity.26 possessed high MDR reversal activity towards doxorubicin-resistant K56/A02 cells. Reversal fold (RF) value reach to 44.26. 26 also increased accumulation of doxorubicin (DOX or ADM) or other MDR-related anticancer drugs with different structures. In conclusion, compound 26 deserves more research for its good features as P-gp inhibitor.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Antibióticos Antineoplásicos/farmacología , Doxorrubicina/farmacología , Diseño de Fármacos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Isoquinolinas/farmacología , Ftalazinas/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antibióticos Antineoplásicos/síntesis química , Antibióticos Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Doxorrubicina/síntesis química , Doxorrubicina/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Isoquinolinas/síntesis química , Isoquinolinas/química , Células K562 , Estructura Molecular , Ftalazinas/síntesis química , Ftalazinas/química , Relación Estructura-ActividadRESUMEN
Copper phthalocyanine (CuPc) nanostructure crystals, including nanoflower, nanoribbon, and nanowire, were controllably fabricated by temperature gradient physical vapor deposition (TG-PVD) through controlling the growth parameters. In a controllable growth system with carrier gas N2, nanoflower, nanoribbon, and nanowire crystals were formed in a high-temperature zone, medium-temperature zone, and low-temperature zone, respectively. They were proved to be ß-phase, coexist of α-phase and ß-phase, and α-phase respectively based on x-ray diffraction results. Furthermore, ultralong CuPc nanowires up to several millimeters could be fabricated by TG-PVD without carrier gas, and they were well-aligned to form large-area CuPc nanowire crystal arrays by the Langmuir-Blodgett method. The nanostructure crystals showed unusual optical absorption spectra from the ultraviolet-visible to near-infrared range, which was explained by the diffraction and scattering caused by the wavelength-sized nanostructures. These CuPc nanostructure crystals show potential applications in organic electronic and optoelectronic devices.