#85 Further structural modification in compound 2e to improve multifunctional properties for the treatment of Alzheimer’s disease (AD)

Abstract

One of the primary goals behind our present work is to improve further the acetylcholinesterase (AChE) inhibition property of compound 2e. The main objective of this study is to carry out further modification on the phenolic OH group of ferulic acid (FA) to improve upon the AChE inhibition activity without compromising antioxidant properties for the management of AD. We rationally selected 2e from our recent work. We modified the phenolic OH group of ferulic acid with N-(methyl or ethyl) benzyl group using a suitable linker. Next, we carried out enzyme inhibitions studies with these compounds. Further investigations such as antioxidant assay (DPPH assay), metal chelation activity, blood-brain barrier permeable assays (PAMPA assay) are ongoing with these compounds to find their potential to act as drug candidates for AD treatment. The compound (F-215) with N-methyl phenyl substitution with suitable linker on phenolic OH group of FA showed prominent AChE enzyme activity IC₅₀ = 0.92 ± 0.50 over 2e IC₅₀ = 2.42 ± 0.32 μM. The compound F-215 shows improved AChE inhibition compared to 2e. The detailed studies will be presented.