Synthesis of Bis-Chalcones and Evaluation of Its Effect on Peroxide-Induced Cell Death and Lipopolysaccharide-Induced Cytokine Production

Abstract

Plant secondary metabolites are important sources of biologically active compounds with wide pharmacological potentials. Among the different classes, the chalcones form integral pharmacologically active agents. Natural chalcones and bis-chalcones exhibit high antioxidant and anti-inflammatory properties in various experiments. Studies are also underway to explore more biologically active bis-chalcones by chemical synthesis of these compounds. In this study, the effects of six synthetic bis-chalcones were evaluated in intestinal epithelial cells (IEC-6); further, the anti-inflammatory potentials were studied in lipopolysaccharide-induced cytokine production in macrophages. The synthesized bis-chalcones differ from each other first of all by the nature of the aromatic cores (functional group substitution, and their position) and by the size of a central alicycle. The exposure of IEC-6 cells to peroxide radicals reduced the cell viability; however, pre-treatment with the bis-chalcones improved the cell viability in these cells. The mechanism of action was observed to be the increased levels of glutathione and antioxidant enzyme activities. Further, these bis-chalcones also inhibited the LPS-stimulation-induced inflammatory cytokine production in RAW 264.7 macrophages. Overall, the present study indicated the cytoprotective and anti-inflammatory abilities of synthetic bis-chalcones.

The Synthesis of 2′-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities

“…Several biological and pharmacological properties are attributed to natural or synthetic chalcones, such as antibacterial [3], antifungal [4], antimalarial [5], anti-inflammatory [6], anti-obesity [7], and antitumor [8] (Figure 1). Chalcones are also reported for inhibiting oxidative radical formation in different in vitro and in vivo models [9] and enhancing antioxidant defense in animals [10]. Chalcones have also been reported to reduce cytokine production and nitric oxide synthase activity in macrophages [6,11] and to regulate prostaglandin synthesis and the NF-kB pathway [12].…”