Characterization of Novel Synthetic Polyphenols: Validation of Antioxidant and Vasculoprotective Activities

Abstract

Antioxidant compounds, including polyphenols, have therapeutic effects because of their anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties. They play important roles in protecting the cardiovascular and neurological systems, by having preventive or protective effects against free radicals produced by either normal or pathological metabolism in such systems. For instance, resveratrol, a well-known potent antioxidant, has a counteracting effect on the excess of reactive oxygen species (ROS) and has a number of therapeutic benefits, like anti-inflammatory, anti-cancer and cardioprotective activities. Based on previous work from our group, and on the most frequent OH substitutions of natural polyphenols, we designed two series of synthetically accessible bis-polyhydroxyphenyl derivatives, separated by amide or urea linkers. These compounds exhibit high antioxidant ability (oxygen radical absorbance capacity (ORAC) assay) and interesting radical scavenging activity (RSA) values (2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and α,α-diphenyl-β-picrylhydrazyl (DPPH) tests). Some of the best polyphenols were evaluated in two biological systems, endothelial cells (in vitro) and whole aorta (ex vivo), highly susceptible for the deleterious effects of prooxidants under different inflammatory conditions, showing protection against oxidative stress induced by inflammatory stimuli relevant in cardiovascular diseases, i.e., Angiotensin II and IL-1β. Selected compounds also showed strong in vivo antioxidant properties when evaluated in the model organism Saccharomyces cerevisiae.

Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing Properties

“…However, one of the main challenges and limitations in the use of polyphenols as chemotherapy adjuvants consists of their poor bioavailability due to their high metabolism rate and quick bodily removal [76]. Thus, the research is now focused on the synthesis of polyphenol-derived compounds to harness their beneficial effects on human health while overcoming this issue [77][78][79].…”

Mechanisms of Action of Fruit and Vegetable Phytochemicals in Colorectal Cancer Prevention

“…For example, polyphen such as quercetin, induce phosphorylation of p38, c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK) proteins [32], which disrupt the regulatio Bcl-2, Bcl-xl, and Bax proteins, thereby releasing cytochrome c and inducing cell apop Polyphenols and flavonoids (complex phenolic acids) can be easily confused with each other due to their structural similarities and phytochemical properties. However, polyphenols are a large family of compounds (>8000) with more than one phenolic group in their chemical structure [27] and are of natural, semi-synthetic, or synthetic origin [28]. Flavonoids are a group of complex phenolic acids that share a common structure of 15carbon skeleton and are of natural origin [29].…”

Construction of Chitosan/Alginate Nano-Drug Delivery System for Improving Dextran Sodium Sulfate-Induced Colitis in Mice

“…It is a nutrient and health compound extracted from natural plants such as grapes, cranberries and peanuts [ 16 , 17 ]. Studies have shown that RES has pharmacological effects, such as scavenging free radicals [ 18 ] and anti-inflammatory [ 19 ] and antioxidant [ 20 ] properties, which can reduce the development of IBD and improve the quality of life of patients with UC. Research by Fang Li et al [ 21 ] also showed that RES can reduce the inflammatory symptoms and tissue damage in the dextran sodium sulfate (DSS)-induced mice colitis model.…”