Biological evaluation, chelation, and molecular modeling studies of novel metal-chelating inhibitors of NF-kappa B-DNA binding: Structure activity relationships

• Tipo: Artigo em Revista Científica Internacional
• Data: 2006

Autores

Sharma, RK (Autor) Outra; Chopra, S (Autor) Outra; Sharma, SD (Autor) Outra; Pande, V (Autor) Outra; Ramos, MJ (Autor) FCUP; Meguro, K (Autor) Outra; Inoue, JI (Autor) Outra; Otsuka, M (Autor) Outra

Revista

Título: Journal of Medicinal Chemistry

Vol. 49

Páginas: 3595-3601

ISSN: 0022-2623

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 19 Citações

Scopus - 18 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-004-K61

DOI: 10.1021/jm050617x

Abstract (EN): Previously, we have reported that aurintricarboxylic acid (ATA) is one of the most potent inhibitors of the DNA binding of transcription factor NF-kappa B. We now report the NF-kappa B-DNA binding inhibitory activity of ATA analogues. An electrophoretic mobility shift assay has shown that bromopyrogallol red (BPR) is the most effective inhibitor of NF-kappa B-DNA binding among the studied analogues. The molecular modeling studies showed that BPR makes a strong network of hydrogen bonds with the DNA-binding region of the p50 subunit of NF-kappa B and has electronegative potential on its peripheral surface. Because zinc has been reported to influence the DNA binding of NF-kappa B, the interaction of these analogues with zinc was studied. Chemical speciation and formation-constant studies showed that BPR forms the most stable 1:1 complex with zinc. BPR has also been found to be the most potent antioxidant among the studied analogues.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7