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

• Type: Article in International Scientific Journal
• Date: 2006

Authors

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

Journal

Title: Journal of Medicinal Chemistry

Vol. 49

Pages: 3595-3601

ISSN: 0022-2623

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 19 Citations

Scopus - 18 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7