Anti-inflammatory effect of synthesized indole-based chalcone (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one: an in vitro and in vivo studies.

Purpose: Chalcones are precursors of flavonoids with a wide range of pharmacological activities. This study evaluates the anti-inflammatory effect of indole based chalcone derivative (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one (IC9) on lipopolysaccharide (LPS) activated murine macrophages RAW264.7 cells and carrageenan-induced acute model in rats.Materials and methods: LPS-treated RAW264.7 cell lines and carrageenan-induced animal model were employed to evaluate the anti-inflammatory activity of IC9. The cell cytotoxicity studies were carried out by MTT assay. Reactive oxygen species (ROS) production and other inflammatory markers such as prostaglandin E2 (PGE2), nitric oxide (NO) as well as cyclooxygenase-2 (COX-2) activity were determined using ELISA. The RT-PCR was performed to determine mRNA expressions in the case of inducible nitric oxide synthase (iNOS), COX-2, Toll-like receptor-4 (TLR-4) and also nuclear translocation of NF-κB activity.Results: LPS-activated RAW264.7 cells showed an increased level of ROS generation and other inflammatory markers such as PGE2, NO level and COX-2 activity. Expression of iNOS, COX- 2 and TLR-4 mRNA expression were also up-regulated along with nuclear translocation of NF-κB. On IC9 supplementation, all the above parameters of LPS-activated cells were found to be reversed, resembling the control group. Moreover, IC9 significantly inhibited paw swelling and exhibited maximum inhibition of 78.45% at low dose of 7.5 mg/kg.bwt.Conclusions: The targeting anti-inflammatory efficacy and profound NF-κB sensitive transcriptional regulatory mechanism of IC9 accounts for its effective anti-inflammatory action.

Imidazole bearing chalcones as a new class of monoamine oxidase inhibitors.

In the present study, series of eleven (2E)-1-[4-(1H-imidazol-1-yl)substituted phenyl]-3-phenylprop-2-en-1-one (IM1-IM11) derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The results indicate that (2E)-3-[4-(dimethylamino) phenyl]-1-[4-(1H-imidazol-1-yl) phenyl] prop-2-en-1-one (IM5) is a nonselective and reversible competitive inhibitor of MAO-A and MAO-B with IC50 values of 0.30 ±â€¯0.010 and 0.40 ±â€¯0.017 µM, respectively ; those of (2E)-1-[4-(1H-imidazol-1-yl) phenyl]-3-(4-methylphenyl) prop-2-en-1-one (IM4) were 1.06 ±â€¯0.090 and 0.32 ±â€¯0.021 µM, respectively. Kinetic studies document that both IM5 and IM4 are competitive inhibitors of MAO-A and MAO-B with Ki value of 0.11 ±â€¯0.0085 and 0.085 ±â€¯0.0064 µM, respectively. Molecular docking studies of lead compounds further explained the binding modes in the inhibitor binding cavity of both MAO-A and MAO-B.