RESUMEN
Four series of carbazole derivatives, including N-substituted-hydroxycarbazoles, oxazinocarbazoles, isoxazolocarbazolequinones, and pyridocarbazolequinones, were studied using diverse biological test methods such as a CE-based assay for CK2 activity measurement, a cytotoxicity assay with IPC-81 cell line, determination of MIC of carbazole derivatives as antibacterial agents, a Plasmodium falciparum susceptibility assay, and an ABCG2-mediated mitoxantrone assay. Two oxazinocarbazoles Ib and Ig showed CK2 inhibition with IC50 = 8.7 and 14.0 µM, respectively. Further chemical syntheses were realized and the 7-isopropyl oxazinocarbazole derivative 2 displayed a stronger activity against CK2 (IC50 = 1.40 µM). Oxazinocarbazoles Ib, Ig, and 2 were then tested against IPC-81 leukemia cells and showed the ability to induce leukemia cell death with IC50 values between 57 and 62 µM. Further investigations were also reported on antibacterial and antiplasmodial activities. No significant inhibitory activity on ABCG2 efflux pump was detected.
Asunto(s)
Antibacterianos/síntesis química , Antimaláricos/síntesis química , Antineoplásicos/síntesis química , Carbazoles/síntesis química , Oxazinas/síntesis química , Inhibidores de Proteínas Quinasas/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antimaláricos/química , Antimaláricos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Carbazoles/química , Carbazoles/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/crecimiento & desarrollo , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/crecimiento & desarrollo , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oxazinas/química , Oxazinas/farmacología , Pruebas de Sensibilidad Parasitaria , Plasmodium falciparum/efectos de los fármacos , Proteína Quinasa C/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
Oxidation of 2- and 3-hydroxycarbazoles with Frémy's salt gave the corresponding ortho-carbazolequinones. These molecules react as carbodienophiles in Diels-Alder reaction with 1-acetoxy-1,3-butadiene and 1,3-cyclopentadiene to provide the novel benzocarbazolequinone structures 15, 16, 18 and 19.