Myeloperoxidase Inhibitory and Antioxidant Activities of (E)-2-Hydroxy-α-aminocinnamic Acids Obtained through Microwave-Assisted Synthesis

Abstract

Myeloperoxidase (MPO) is an enzyme present in human neutrophils, whose main role is to provide defenses against invading pathogens. However, highly reactive oxygen species (ROS), such as HOCl, are generated from MPO activity, leading to chronic diseases. Herein, we report the microwave-assisted synthesis of a new series of stable (E)-(2-hydroxy)-α-aminocinnamic acids, in good yields, which are structurally analogous to the natural products (Z)-2-hydroxycinnamic acids. The radical scavenging activity (RSA), MPO inhibitory activity and cytotoxicity of the reported compounds were evaluated. The hydroxy derivatives showed the most potent RSA, reducing the presence of DPPH and ABTS radicals by 77% at 0.32 mM and 100% at 0.04 mM, respectively. Their mechanism of action was modeled with BDEOH, IP and ΔEH-L theoretical calculations at the B3LYP/6 − 31 + G(d,p) level. Compounds showed in vitro inhibitory activity of MPO with IC50 values comparable to indomethacin and 5-ASA, but cytotoxicities below 15% at 100–200 µM. Docking calculations revealed that they reach the amino acid residues present in the distal cavity of the MPO active site, where both the amino and carboxylic acid groups of the α-aminopropenoic acid arm are structural requirements for anchoring. (E)-2-hydroxy-α-aminocinnamic acids have been synthesized for the first time with a reliable method and their antioxidant properties demonstrated.

Dietary supplementation with Macleaya cordata extract alleviates intestinal injury in broiler chickens challenged with lipopolysaccharide by regulating gut microbiota and plasma metabolites

“…The results of Spearman correlation analysis of gut microbiota and plasma metabolites showed that the relative abundance of Firmicutes was positively correlated with the level of 2-hydroxycinnamic acid, a well-known antioxidant ( 73 , 74 ), suggesting that Firmicutes could exert antioxidant function by increasing the level of 2-Hydroxycinnamic acid. Corynebacterium plays a pathogenic role by secreting phospholipase D (PLD) and diphtheria toxin, and PLD can activate NF-κB in epithelial cells, release inflammatory factors such as IL-6, and increase vascular permeability ( 75 ).…”

In Silico and In Vitro Studies of Benzothiazole-Isothioureas Derivatives as a Multitarget Compound for Alzheimer’s Disease

“…The results were expressed as percentage of DPPH radical reduced (antioxidant activity) for each concentration of the selected compounds. The percentage of the DPPH radical reduced was calculated using the following equation: [1 − ((A 1 − A 2 )/(A DPPH − A S ))] × 100, where: A 1 = Absorbance of the compound with DPPH, A 2 = Absorbance of the compound plus DMSO: methanol, A DPPH = Absorbance of DPPH (diluted 1:1 with DMSO: methanol) and A S = Absorbance of DMSO: methanol [ 61 ].…”

“…The reaction was incubated for 30 min at room temperature protected from light. The absorbance was recorded at 734 nm in a transparent 96-well test microplate (Multiskan-EX Thermo Scientific) [ 61 ].…”

Dihydropyrazole-Carbohydrazide Derivatives with Dual Activity as Antioxidant and Anti-Proliferative Drugs on Breast Cancer Targeting the HDAC6

“…The radical scavenging activity (RSA) of 2a-i was assessed by the DPPH test, using ascorbic acid (AA) as control. This assay is widely used to evaluate the antioxidant capabilities of natural and synthetic compounds, where DPPH is the free radical which can accept an electron or hydrogen atom and become reduced [82]. The results are shown in Figure 7a; all compounds exhibited antioxidant activities above 75% at 100 µM, with 2c, 2e, 2h, and 2i being the most active (up to 90%) and similar to AA (93%).…”