RESUMEN
The reaction of 6-amino-1,3-dimethylpyrimidine-2,4[1H,3H]-dione [1] as a binucleophile with primary aromatic or heterocyclic amines and formaldehyde or aromatic [heterocyclic] aldehydes in a molar ratio [1:1:2] gave the pyrimido[4,5-d]pyrimidin-2,4-dione ring systems 2-5. Treatment of 1 with diamines and formalin in molar ratio [2:1:4] gave the bis-pyrimido[4,5-d]pyrimidin- 2,4-diones 6-8. Furthermore, substituted pyrimido[4,5-d]pyrimidin-2,4-diones with uracil derivative 11 or spiro indole 16 were synthesized. Synthesis of pyrimido[4,5-d]pyrimidin-2,4-diones with different substitution at C-5 and C-7 was achieved to give 13 and 18, respectively
Asunto(s)
Digitonina/química , Semicarbacidas/química , Iminas/química , Diaminas , Formaldehído/químicaRESUMEN
Tumor migration/invasion is the main cause of tumor progression and STAT3 is needed to enhance tumor migration/invasion by up-regulating MMP-9. Thus, agents that inhibit STAT3 activation may be used as an anticancer drug. We present herein that 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol- 4-one (LYR71) , a derivative of trimeric resveratrol, has an anticancer activity through inhibition of STAT3 activation. We found that LYR71 suppressed STAT3 activation and inhibited the expression and activity of MMP-9 in RANTES-stimulated breast cancer cells. In addition, LYR71 reduced RANTES-induced MMP-9 transcripts by blocking STAT3 recruitment, dissociating p300 and deacetylating histone H3 and H4 on the MMP-9 promoter. Furthermore, LYR71 inhibited tumor migration/invasion in RANTES-treated breast cancer cells and consequently blocked tumor progression in tumor-bearing mice. Taken together, the results of this study suggest that LYR71 can be therapeutically useful due to the inhibition effect of STAT3-mediated MMP-9 expression in breast cancer cells.
Asunto(s)
Animales , Femenino , Humanos , Ratones , Antineoplásicos/química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Western Blotting , Neoplasias de la Mama/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Inmunoprecipitación de Cromatina , Expresión Génica/efectos de los fármacos , Iminas/química , Inmunohistoquímica , Neoplasias Mamarias Experimentales/patología , Metaloproteinasa 9 de la Matriz/genética , Ratones Endogámicos BALB C , Ratones Desnudos , Estructura Molecular , Fosforilación/efectos de los fármacos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT3/genética , Estilbenos/química , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
The nitrile imine generated by the action of triethylamine on 2-bromo-1-benzofurylglyoxal-2-[3 phenylpyrazol 5-yl]-hydrazone reacted with some Schiff bases, -nitrostyrenes and thiocarboxamidocinnamonitrile derivatives via dipolar cycloaddition reactions to yield several new polyfunctional pyrazole and 1,2,4-triazole derivatives. Structures were confirmed by elemental analysis and spectral data studies
Asunto(s)
Pirazoles/análogos & derivados , Triazoles/síntesis química , Nitrilos/química , Iminas/químicaRESUMEN
A variety of new pyrazole, pyrrolinopyrazole and pyrazolopyridazine derivatives were synthesised via the dipolar cycloaddition reactions of acrylonitrile, ethyl acrylate and N-arylmaleimides with the nitrile imine regenerated from 2-bromo-1- benzofurylglyoxal-2-[3-phenylpyrazol-5-yl]-hydrazone. Structure of the newly synthesized derivatives were established on the basis of elemental analysis and spectral data