Synthesis and Anti-inflammatory Effect of Chalcones

Abstract

The process of degranulation of mast cells and neutrophils contributes to inflammatory disorders. Activation of microglial cells and macrophages is believed to be involved in inflammatory, infectious and degenerative diseases of the CNS. Combining the potent inhibition of chemical mediators released by the degranulation of mast cells or neutrophils and from the activated microglial cells or macrophages, would lead to a promising anti-inflammatory agent for the treatment of peripheral and central inflammation. A series of chalcone derivatives have been reported to have potent anti-inflammatory activity. In an effort to continually develop potent anti-inflammatory agents, novel series of chalcones, 2'-hydroxy- and 2',5'-dihydroxychalcones were synthesized and their inhibitory effects on the activation of mast cells, neutrophils, microglial cells and macrophages were evaluated in-vitro. The chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with an appropriate aromatic aldehyde. The alkoxychalcones were prepared with appropriate hydroxychalcones and alkyl iodide and the dihydroxychalcones were prepared by hydrogenation of an appropriate chalcone with Pd/C. Almost all of the hydroxychalcones exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB). Of the hydroxychalcones, compound 1 was the most potent inhibitor of the release of beta-glucuronidase (IC50=1.6+/-0.2 microM) and lysozyme (IC50=1.4+/-0.2 microM) from rat neutrophils stimulated with fMLP/CB. Almost all of the 2',5'-dialkoxychalcones exhibited potent inhibitory effects on nitric oxide (NO) formation from murine microglial cell lines N9 stimulated with lipopolysaccharide (LPS). Of these, compound 11 showed the greatest effect (IC50=0.7+/-0.06 microM). The present results demonstrated that most of the chalcone derivatives have an anti-inflammatory effect. The inhibitory effects of dialkoxychalcones, 10-12 on inflammation are probably not due to the inhibition of mast cells and neutrophil degranulation, but are mediated through the suppression of NO formation from N9 cells.

Study of the antiproliferative potential of seed extracts from Northeastern Brazilian plants

“…Previously, it was demonstrated that hydroalchoolic stem bark extracts from M. urundeuva exert anti-inflammatory effects attributed to chalcones , Souza et al 2007), a compound belonging to the group of flavonoids naturally found in fruits, flowers, vegetables, teas and wines (Abdulla andGruber 2000, Ferreira et al 2008). Besides the traditional antioxidant properties attributed to the flavonoids, some chalcones and their derivatives have reported to be potent cyclooxygenase inhibitors (Hsieh et al 1998). This is an important approach to some kinds of cancers, since COX-2 blockage avoids the expression of NF-κB activation, a key nuclear transcription factor involved in controlling inflammation and tumorigenesis (Surh et al 2001), since inflammation has been frequently found in premalignant lesions (Dranoff 2004).…”

Synthesis and in vitro anticancer evaluation of 1,4-phenylene-bis-pyrimidine-2-amine derivatives

“…21−23 Moreover, various drugs containing a pyrimidine nucleus like 5-fluorouracil (5-FU), tegafur, and thioguanine were prepared and used as anticancer agents. 24,25 Chalcones are known to show different biological activities, such as antioxidant, 26 antiinflammatory, 27 antimalarial, 28 antileishmanial, 29 anticancer, 30 and antitumor 31 activities.…”

Crystal Structure Studies and Thermal Characterization of Novel 4-Hydroxychalcone Derivative

“…Chalcones are a class of compounds mostly studied for pharmacological properties 10,11 and recently have been explored for their optical applications [12][13][14][15] . In the past few years chalcones have been shown to possess interesting biological properties like anti-invasive 16 , anticancer 17,18 , antimalarial 19 , antimicrobial 20 , antimutagenic 21 , radioprotective 22 , anti-inflammatory effects 23 and find use as synthetic intermediates 24 .…”