Studies of synthetic chalcone derivatives as potential inhibitors of secretory phospholipase A₂, cyclooxygenases, lipoxygenase and pro-inflammatory cytokines

Abstract

Arachidonic acid metabolism leads to the generation of key lipid mediators which play a fundamental role during inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as a synergistic anti-inflammatory effect with enhanced spectrum of activity. A series of 1,3-diphenyl-2-propen-1-one derivatives were investigated for anti-inflammatory related activities involving inhibition of secretory phospholipase A₂, cyclooxygenases, soybean lipoxygenase, and lipopolysaccharides-induced secretion of interleukin-6 and tumor necrosis factor-alpha in mouse RAW264.7 macrophages. The results from the above mentioned assays exhibited that the synthesized compounds were effective inhibitors of pro-inflammatory enzymes and cytokines. The results also revealed that the chalcone derivatives with 4-methlyamino ethanol substitution seem to be significant for inhibition of enzymes and cytokines. Molecular docking experiments were carried out to elucidate the molecular aspects of the observed inhibitory activities of the investigated compounds. Present findings increase the possibility that these chalcone derivatives might serve as a beneficial starting point for the design and development of improved anti-inflammatory agents.

Keywords:

• anti-inflammatory
• tumor necrosis factor-alpha
• lipopolysaccharides
• molecular docking

Acknowledgments

This work was supported by the Research Incentive Fund of Universiti Kebangsaan Malaysia (Grant no UKM-DLP-2013-013).

Disclosure

The authors declare no conflicts of interest in this work.