Chalcones as Scavengers of HOCl and Inhibitors of Oxidative Burst: Structure-Activity Relationship Studies

Abstract

Aims: Evaluate the ability of chalcones to scavenge hypochlorous acid (HOCl) and modulate oxidative burst. Background: The chemistry of chalcones has long been a matter of interest to the scientific community due to the phenolic groups often present and to the various replaceable hydrogens that allow the formation of a broad number of derivatives. Due to this chemical diversity, several biological activities have been attributed to chalcones, namely anti-diabetic, anti-inflammatory and antioxidant. Objectives: Evaluate the ability of a panel of 34 structurally related chalcones to scavenge HOCl and/or suppress its produc-tion through the inhibition of human neutrophils’ oxidative burst, followed by the establishment of the respective structure-activity relationships. Methods: The ability of chalcones to scavenge HOCl was evaluated by fluorimetric detection of the inhibition of dihydro-rhodamine 123 oxidation. The ability of chalcones to inhibit neutrophils’ oxidative burst was evaluated by chemiluminomet-ric detection of the inhibition of luminol oxidation. Results: It was observed that the ability to scavenge HOCl depends on the position and number of hydroxy groups on both aromatic rings. Chalcone 5b was the most active with an IC50 value of 1.0 ± 0.1 μM. The ability to inhibit neutrophils’ oxi-dative burst depends on the presence of a 2’-hydroxy group on A-ring and on other substituents groups, e.g. methoxy, hy-droxy, nitro and/or chlorine atom(s) at C-2, C-3 and/or C-4 on B-ring, as in chalcones 2d, 2f, 2j, 2i, 4b, 2n and 1d, which were the most actives with IC50 values ranging from 0.61 ± 0.02 μM to 1.7 ± 0.2 μM. Conclusion: The studied chalcones showed high activity at a low micromolar range, indicating their potential as antioxidant agents and to be used as a molecular structural scaffold for the design of new anti-inflammatory compounds.

Different Strategies to Attenuate the Toxic Effects of Zinc Oxide Nanoparticles on Spermatogonia Cells

“…In previous a work, among many other synthetic chalcones that were studied, chalcone 1 was one of the most active chalcones in modulating the exacerbated production of ROS during neutrophils oxidative burst [ 10 ]. This activity was attributed to the lipophilicity of this chalcone, which facilitates membrane transport and the binding of this compound to intracellular targets.…”

“…For the second strategy treatment, cells were plated at a density of 250,000 cells/well in 6-well plates and pre-treated with various concentrations of chalcone 1 (1.6, 3.1, 6.25, and 12.5 µM) for 1 h prior exposure to ZnO NPs (20 µg/mL), and both chalcone 1 and ZnO NPs were left for 6 and 12 h ( Supplementary Figure S5B ). The chalcone 1 concentrations were chosen based on previous studies using these types of compounds as inhibitors of oxidative burst [ 10 ]. For further information, please see the concentrations used for chalcone 4b (same structure as chalcone 1 ) in the referred study.…”

“…However, few studies have described the toxicity and protective effects of antioxidants against ZnO NPs in cells from the early stages of spermatogenesis. Some studies have indicated that chalcones may have antioxidant properties due to their free radical scavenging activities [ 10 ]. Chalcones (1,3-diarylprop-2-en-1-ones) are natural products with a wide distribution in different plant families belonging to the flavonoid group [ 11 , 12 ].…”

“…Additionally, several research articles have been published regarding the synthesis of novel chalcones derivatives and the investigation of their pharmacological activities. Two examples among a huge number of articles are, e.g., the study developed by Rocha et al that synthesized a wide range of chalcone derivatives and evaluated their ability to inhibit the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase to be used as antidiabetic agents [ 19 ], and that of Martins et al, who synthesized several families of chalcones and investigated their potential as scavengers of HOCl and as inhibitors of oxidative burst [ 10 ].…”

Hydroxy Chalcones and Analogs with Chemopreventive Properties

“…A pentahydroxy-substituted chalcone bearing hydroxy groups on the both A and B rings (compound 42 , Table 4 ) has been found to be an efficient HOCl scavenger [ 98 ]. This compound has shown high antioxidant activity, with an IC 50 value of 1 μM.…”