Drug discovery for multifactorial diseases such as Alzheimer's disease (AD) faces limitations with single-target drugs, driving interest in multitarget-directed ligands (MTDLs). Polyamines, proposed as "universal templates" in 1988 due to their ability to interact with multiple receptors (e.g., benextramine for α-adrenoreceptors, muscarinic, and nicotinic receptors), serve as a versatile scaffold for drug design via structural modifications. The universal template approach enabled the development of selective single-target drugs, such as methoctramine and tripitramine for muscarinic receptor subtypes. Extending to MTDL strategy, polyamines are modified to incorporate pharmacophores targeting multiple AD-related pathways. For example, memoquin (8) was designed by replacing the flexible spacer of caproctamine (a polyamine acting on acetylcholinesterase (AChE) and muscarinic M2 receptors) with a 1,4-benzoquinone moiety (antioxidant). In vitro studies showed memoquin potently inhibits AChE (10-fold more potent than donepezil), prevents AChE-induced and self-mediated amyloid-β (Aβ) aggregation, inhibits β-secretase, and acts as a substrate for NAD(P)H/quinone oxidoreductase 1 (NQO1) with antioxidant activity. These findings highlight the potential of polyamines as leads for MTDL development, offering a promising approach to treat multifactorial pathologies like AD with unmet clinical needs.