Future Directions in Polyphenol Synthesis for the Treatment of Neuropathic Pain

Polyphenols, which exhibit numerous bioactivities, have a highly important role in ethnopharmacology, which is the basis of many therapeutic applications. Although natural polyphenols are limited by variability in sources, poor stability, and low bioavailability, innovative approaches in polyphenol synthesis are needed. This chapter proposes future directions in the design, synthesis, and application of bioactive polyphenols, building on the two ends of the spectrum of microbiological wisdom. Although polyphenols are readily found in nature, the synthetic biology, cheminformatics, and nanotechnology that make it possible provide unprecedented opportunities to engineer polyphenols with improved properties. Improving molecular stability, targeting specific biological pathways, and optimizing pharmacokinetics to treat neuropathic pain and chronic diseases. Finally, computational modelling and artificial intelligence are integrated to accelerate the discovery of novel polyphenol analogs for targeted therapeutic applications. Another contribution of this chapter relates to the potential of hybrid polyphenol systems (the integration of natural and synthetic approaches) to strike the best balance between efficacy and sustainability. These include chemicobiological trends, for example, green chemistry in synthesis and use of renewable resources, to address environmental and scalability issues. Through the synthesis of future polyphenols, future polyphenols aim to bridge already-existing, yet still unresolved, challenges with new and, perhaps, extreme therapeutic possibilities. However, this transformative approach not only furthers the cause of ethnopharmacology but also provides an otherwise unprecedented, sustainable basis for future generations of polyphenol-based therapeutics.