Multifunctional Hybrid Sulfonamides as Novel Therapeutic Agents for Alzheimer’s Disease

<b>Aim:</b> A breakthrough in modern medicine, in terms of treatment of Alzheimer's disease, is yet to be seen, as the scene is currently plagued with numerous clinical trial failures. Here, we are exploring multifunctional hybrid sulfonamides for their anti-Alzheimer activity due to the complex nature of the disease. <b>Results & methodology:</b> Compound 41 showed significant inhibition of MMP-2 (IC₅₀: 18.24 ± 1.62 nM), AChE (IC₅₀: 4.28 ± 0.15 μM) and BuChE (IC₅₀: 1.32 ± 0.02 μM). It also exhibited a metal-chelating property, as validated by an <i>in vitro</i> metal-induced Aβ aggregation assay using confocal fluorescence imaging. Whereas, MTT and DPPH assays revealed it to be nontoxic and neuroprotective with substantial antioxidant property. <b>Conclusion:</b> The present study puts forth potent yet nontoxic lead molecules, which foray into the field of multitargeted agents for the treatment of Alzheimer's disease.