Jalil_2024_RSC.Adv_14_8905

Alzheimer's disease (AD) is a multifactorial irreversible neurological disorder with multiple enzymes involved. In the treatment of AD, multifunctional agents targeting cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors have shown promising results. Herein, a series of novel quinoline-sulfonamides (a1-18) were designed and synthesized as a dual inhibitor of MAOs and ChEs. The in vitro results showed that compounds a5, a12, a11, and a6 exhibited the most potent compounds against specific enzymes. They had IC(50) value 0.59 +/- 0.04 for MAO-A, 0.47 +/- 0.03 for MAO-B, 0.58 +/- 0.05 for BChE and 1.10 +/- 0.77 for AChE microM respectively. Furthermore, kinetic studies revealed that these compounds are competitive. Molecular docking studies enhanced the understanding of the in silico component, unveiling critical interactions, specifically the hydrogen bonding interaction, Pi-Pi, Pi-alkyl, Pi-amid and Pi-sulfur interactions between the ligand and enzymes. These findings suggest that compounds a5, a6, a11, a12, a15, and a18 may be potent multifunctional candidates for AD treatment.