RESUMEN
A series of naphthoimidazoles derivatives (3a-3f) were tested for potential anti-inflammatory activity on lipopolysaccharide (LPS)-treated macrophages. Naphthoimidazole 3e exhibited significant inhibitory effects on nitric oxide (NO) production (IC50 <10µM) and decreased the expression of nitric oxide synthase-2 (NOS-2) and cycloxygenase-2 (COX-2) enzymes. It also inhibited the activation of transcription factor NF-κB. Naphthoimidazole 3e might represent a starting point for the synthesis of new anti-inflammatory naphthoimidazoles derivatives.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Ciclooxigenasa 2/metabolismo , Imidazoles/farmacología , Macrófagos/efectos de los fármacos , FN-kappa B/antagonistas & inhibidores , Naftoquinonas/farmacología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico/antagonistas & inhibidores , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Relación Dosis-Respuesta a Droga , Humanos , Imidazoles/síntesis química , Imidazoles/química , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Estructura Molecular , FN-kappa B/metabolismo , Naftoquinonas/síntesis química , Naftoquinonas/química , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/metabolismo , Relación Estructura-ActividadRESUMEN
In this study, a series of new 4,4'-diaminotriphenylmethanes was efficiently synthesized from aromatic aldehydes and 2,5-dimethoxybenzenamine under microwave irradiation in the presence of Sc(OTf)3 as a catalyst. Antiproliferative activity was assessed by using the MCF-7 estrogen receptor (ER)-positive breast cancer cell line, and antagonist/agonist transcriptional activities were determined. Docking studies and competition studies of triphenylmethanes and radiolabeled estradiol determined that these compounds do not bind the ER, indicating that triphenylmethane-induced changes in proliferative and transcriptional activities differ from conventional mechanisms of action triggered by other selective ER modulators.
