Catechol-based polyphenols

Catechol-based polyphenols are a broad class of secondary plant metabolites defined by the presence of a catechol functional group, which consists of a benzene ring with two adjacent hydroxyl groups [1, 12]. Found in abundance in dietary sources such as tea, fruits, and vegetables, these compounds include well-known flavonoids like quercetin and green tea catechins like epigallocatechin gallate (EGCG) [3, 6]. Biologically, they function as pleiotropic ligands that interact with multiple molecular targets, including signaling proteins (e.g., Keap1), metabolic enzymes (e.g., COMT), and structural proteins (e.g., beta-actin), rather than acting as a single receptor or enzyme [1, 10]. These molecules are prized for their antioxidant, anti-inflammatory, and neuroprotective properties, though their therapeutic efficacy is often limited by poor metabolic stability and low systemic bioavailability [6, 15]. In the context of drug development, they are frequently explored as scaffolds for designing inhibitors of protein aggregation or as modulators of oxidative stress pathways. Because 'catechol-based polyphenols' refers to a chemical class of ligands rather than a specific biological target molecule, the term is categorized as incorrect in the context of identifying a single therapeutic target [2, 12].

Other names

Catechol polyphenolsOrtho-diphenolic compoundsCatechol-type polyphenolsCatechol-containing flavonoids

Catechol-based polyphenols primarily act by scavenging reactive oxygen species (ROS) and chelating transition metal ions like iron and copper to prevent oxidative damage [3, 11, 16]. They also undergo oxidation to form electrophilic o-quinones that covalently modify protein cysteine residues, such as those on the Keap1 scaffold protein, thereby activating cytoprotective pathways like Nrf2 [1]. Furthermore, they can inhibit specific enzymes including catechol-O-methyltransferase (COMT), matrix metalloproteinases (MMPs), and prevent protein aggregation, such as alpha-synuclein [1, 12].