Design, Synthesis, and <i>In Vitro</i> and <i>In Silico</i> Approaches of Novel Indanone Derivatives as Multifunctional Anti-Alzheimer Agents

Alzheimer’s disease (AD) is a neurological, progressive illness that typically affects the elderly and is clinically distinguished by memory and cognitive decline. Due to a number of factors, including the absence of a radical treatment, an increase in the patient population over time, the high cost of care and treatment, and a significant decline in patients’ quality of life, the importance of this disease has increased. These factors have all prompted increased interest among researchers in this field. The chemical structure of the donepezil molecule, the most popular and effective treatment response for AD, served as the basis for the design and synthesis of 42 novel indan-1-one derivatives in this study. Using IR, ¹H, and ¹³C NMR as well as mass spectroscopic techniques, the compounds’ structures were identified. Research on the compounds’ antioxidant activities, cholinesterase (ChE) enzyme inhibition, monoamine oxidase (MAO) A and B inhibitory activities, β-amyloid plaque inhibition, and cytotoxicity impact was carried out. Inhibition of β-amyloid plaque aggregation; effective inhibition of AChE, BChE, and MAO-B enzymes; and significant antioxidant activity were all demonstrated by compounds <b>D28</b>–<b>D30</b> and <b>D37</b>–<b>D39</b>. Because of their various actions, it was hypothesized that the related compounds may be useful in treating AD symptoms as well as providing palliative care.