4’4 bromophenyl 4’piperidinol Derivatives as a Multifactorial anti -Alzheimer agent: Synthesis, In Vitro, and In- Silico based Studies

Abstract: 4’4 bromophenyl 4’piperidinol derivatives were synthesized, and evaluated as multifactorial agents for the treatment of Alzheimer’s disease (AD). Among all the analogues, AB11 and AB14 showed the best activity against acetylcholinesterase (AChE) with IC₅₀ = 0.029 μM and 0.038 μM respectively. Both compounds also acted as a good antioxidant agents (IC₅₀ = 26.38 μM for AB11 and 23.99 μM for AB14) while AB11 is the only molecule that displayed moderate inhibition of amyloid beta (Aβ) (43.25% at 500 μM). AB11 and AB14 were found selective against monoamine oxidase-B (MAO-B) with IC₅₀ values of 866 μM and 763 μM respectively. AB10, AB17, and AB70 exhibited activity against both MAO-A and MAO-B and showed inhibitory potential against acetylcholinesterase, moreover, all analogues are capable of disassembling the well-structured Aβ fibril. Molecular modeling of selected compounds displayed interactions with the active site of human MAO-B and AChE enzyme. The results suggested that AB11 is a promising multi-target hit that can be optimized further as a successful drug molecule for the treatment of AD.