RESUMO
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.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 2/metabolismo , Imidazóis/farmacologia , Macrófagos/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Naftoquinonas/farmacologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Relação Dose-Resposta a Droga , Humanos , Imidazóis/síntese química , Imidazóis/química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Estrutura Molecular , NF-kappa B/metabolismo , Naftoquinonas/síntese química , Naftoquinonas/química , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Relação Estrutura-AtividadeRESUMO
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.
