Deoxyvasicinone hybrids in the management of Alzheimer's disease: Recent advances on manmade derivatives, pharmacological activities, and structure-activity relationship.

Abstract

Alzheimer's disease (AD) is a prevalent neurological illness that affects over 80% of aged adults globally in cases of dementia. Although the exact pathophysiological causes of AD remain unclear, its pathogenesis is primarily driven by several distinct biochemical alterations: (i) the accumulation of toxic Aβ plaques, (ii) the hyperphosphorylation of tau proteins, (iii) oxidative stress resulting in cell death, and (iv) an imbalance between the two main neurotransmitters, glutamate and acetylcholine (ACh). Currently, there are very few medications available and no treatment. Presently marketed medications include memantine, an N-methyl-d-aspartate receptor (NMDA) antagonist, and acetylcholinesterase (AChE) inhibitors: rivastigmine, donepezil, and galantamine. Unfortunately, these medications are only useful in the initial stages of AD. The mentioned medications only provide symptomatic relief and do not slow down the disease progression in the advanced stages. Therefore, there is an urgent need to develop potential candidates to treat AD, symptomatically and therapeutically. Many research groups focus on natural products due to their diverse therapeutic profiles and easy availability. One such natural product is deoxyvasicinone, isolated from Adhatoda vasica. Given its broad pharmacological profile, various researchers have developed semisynthetic hybrids of deoxyvasicinone to address multifaceted diseases like AD. In this review article, we tried to summarize the semisynthetic hybrids of deoxyvasicinone developed over the past decade (2014-2024) for managing AD. We focus on their design, pharmacological activity, and structure-activity relationship (SAR) analysis. We hope this review enhances the reader's understanding of future exploratory options for deoxyvasicinone hybrids in AD management.