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.

Glutathione S‐transferase omega 1 inhibition activates JNK‐mediated apoptotic response in breast cancer stem cells

“…Earlier reports suggest binding of chalcones to molecular targets such as HIF1α , phospholipase A2 and tubulin polymerization in cancer cells. In our molecular docking study, we observed that the R‐configuration (Fig.…”

Effects of chalcone derivatives on players of the immune system

“… 72 3-(2,3-dimethoxy-phenyl)-1-naphthalene-1-yl-propenone ( 34 ) and 4-(4-diethylamino-phenyl)-1,1-diphenyl-but-3-en-2-one ( 35 ) were also reported to suppress the secretion of IL-6 and TNF-α in LPS-induced RAW 264.7 macrophages. 73 Two β-chlorovinyl chalcones, with chemical structures of 5-(4-bromo-phenyl)-5- chloro-1-(4-methoxy-phenyl)-penta-2,4-dien-1-one ( 36 ) and 5-chloro-5-(4-chloro-phenyl)-1-(4-methoxy-phenyl)-1-penta-2,4-dien-1-one ( 37 ), also exhibited significant suppression of LPS-induced IL-6 and TNF-α production in THP-1 cells. 74 Okanin ( 38 ), a natural chalcone isolated from the genus Bidens and 3-penten-2-one were found to be able to suppress LPS-induced NO production and iNOS expression in RAW264.7 macrophages through upregulation of HO-1 expression.…”

Structure Based Library Design (SBLD) for new 1,4-dihydropyrimidine scaffold as simultaneous COX-1/COX-2 and 5-LOX inhibitors

“…13,14 It is also noted from literature that the inhibition of more than one enzyme involved in different pathways of arachidonic acid metabolism lead to a synergistic anti-inflammatory effect with enhanced spectrum of activity. [15][16][17] The virtual combinatorial library is generated routinely for small molecules during the drug discovery cycle and screened based on their predicted physicochemical properties, activities, specificities, etc. [18][19][20] The virtual screening is useful in selecting a smaller set of promising hits from a large set of compound libraries.…”