Polyphenol: Development of Polyphenol-Inspired Derivatives Targeting Pathological Factors of AD

Abstract

Alzheimer’s disease (AD) is the most common type of dementia having a complex pathophysiology with no disease modifying treatments available in clinics. Polyphenolic compounds, a class of natural plant compounds, have been extensively studied for their potential therapeutic use in AD. The neuroprotective, antioxidant, as well as anti-inflammatory properties exhibited by these compounds are important in the treatment and management of AD. Phenolic compounds can inhibit the formation and aggregation of toxic proteins that are implicated in the disease, as well as promote their clearance from the brain. The anti-inflammatory effects of phenolic compounds are significant because chronic inflammation in the brain is thought to contribute to the development and advancement of AD. Additionally, phenolic compounds have been shown to improve cerebral blood flow and enhance neuronal signaling, which can help to improve cognitive function in AD patients. Due to their potential therapeutic efficacy, polyphenols are a key focus in medicinal chemistry for designing multi-targeted as well as single-targeted drug ligands against different therapeutic targets of AD. In this chapter, we have aimed to provide an overview of the synthesis and pre-clinical evaluation of polyphenol derivatives for their potential applications in the management of AD. A short summary of clinical trials performed on polyphenols is also given, followed by design and synthesis of novel derivatives using multiple chemical modification strategies, including naturally inspired derivatives, to further enhance the therapeutic potential of these compounds. Overall, the potential therapeutic effects of phenolic compounds in ameliorating the AD pathophysiology make them an attractive class of natural products holding great promise for the development of therapeutics for this deadly disease. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.