Engineering the Next Generation of Polyphenols: From Natural Bioactives to Multi-Target Therapeutics
Dr. Angela Corvino will present on the strategic topic: Engineering the Next Generation of Polyphenols: From Natural Bioactives to Multi-Target Therapeutics at Polyphenols Applications 2026 which will be held in Malaga, Spain on October 8-9.
Complex diseases are driven by interconnected pathological pathways that cannot always be adequately controlled through single-target therapy. Multi-target strategies therefore offer a promising approach by simultaneously modulating complementary mechanisms. Asthma is a paradigmatic complex disease characterized by oxidative stress, inflammation, mucus hypersecretion, airway hyperresponsiveness, and structural remodeling. Within this context, natural polyphenols represent attractive starting points for multifunctional drug design. Resveratrol (RESV) combines antioxidant and anti-inflammatory activities, but its clinical translation is limited by poor bioavailability, instability, and rapid metabolism. We therefore developed R-TBZ, a hybrid combining RESV with 4-hydroxythiobenzamide, a slow-releasing hydrogen sulfide donor.
R-TBZ was synthesized by microwave-assisted esterification, characterized, and evaluated in bronchial epithelial cells, lung fibroblasts, and ovalbumin-sensitized BALB/c mice.
R-TBZ enhanced mitochondrial antioxidant defenses, reduced mucus production and pro-inflammatory cytokines, and inhibited epithelial–mesenchymal transition and TGF-β-induced fibroblast activation. In allergic mice, it improved lung function, reduced airway hyperresponsiveness, restored β₂-agonist responsiveness, attenuated eosinophilic inflammation, Th2 cytokines, and IgE levels, and limited airway remodeling more effectively than RESV alone.
In conclusion, R-TBZ illustrates how molecular hybridization can expand the therapeutic potential of natural polyphenols, generating a multi-target profile for complex diseases such as asthma, while overcoming key limitations of the parent compound.
