Engineering the Next Generation of Polyphenols: From Natural Bioactives to Multi-Target Therapeutics

Angela Corvino, University of Naples Federico II, Italy

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 therapies. 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. To expand its therapeutic potential, R-TBZ was developed as a molecular 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. Across cellular and in vivo models, R-TBZ showed a broad multi-target profile, enhancing antioxidant defenses while reducing inflammatory responses, mucus production, and processes associated with airway remodeling. In allergic mice, these effects translated into improved lung function, reduced airway hyperresponsiveness, and an overall attenuation of the asthmatic phenotype. Notably, R-TBZ showed enhanced effects compared with RESV alone, highlighting the potential of molecular hybridization to expand the therapeutic profile of natural polyphenols and support their development as multi-target therapeutics for complex diseases such as asthma.

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