1,2-Diaryl-2-hydroxyiminoethanones as Dual COX-1 and beta-Amyloid Aggregation Inhibitors: Biological Evaluation and In Silico Study

IRANNEJAD H., Tan O., Ozadali K., DADASHPOUR S., Kucukkilinc T. T., AHANGAR N., ...More

CHEMICAL BIOLOGY & DRUG DESIGN, vol.85, no.4, pp.494-503, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 85 Issue: 4
  • Publication Date: 2015
  • Doi Number: 10.1111/cbdd.12435
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.494-503
  • Hacettepe University Affiliated: Yes


To find out new agents for treating inflammatory-involved diseases such as Alzheimer's disease, a series of 1,2-diaryl-2-hydroxyiminoethanones containing vicinal diaryl pharmacophore of COX inhibitors were tested by a set of in vitro, in vivo, and computational studies. The in vivo study of compounds indicated their prominent anti-inflammatory ability at the doses of 10 and 20mg/kg comparable to celecoxib (10mg/kg). Further in vitro COX-1/COX-2 evaluations revealed that 4-methoxy derivative 3 had a high selective COX-1 inhibitory activity (COX-1, IC50=0.12m, SI>833). To evaluate their potential use against Alzheimer's disease, in vitro evaluation of -amyloid fibril formation using A((1-40)) and A((1-42)) peptides was performed. The evaluation of their antiaggregation ability gave impressive results and comparable to rifampicin and indomethacin. Conformational study of compound 3 and subsequent docking of its restrained analogs on both active sites of COX-1 and COX-2 could provide a proof of its COX-1 selectivity as well as molecular dynamic simulation could elucidate and give more insight into the amyloid disaggregation mechanisms leading to rational design of inhibitors.