Screening of Some Sulfonamide and Sulfonylurea Derivatives as Anti-Alzheimer's Agents Targeting BACE1 and PPARγ

In the last few decades, Alzheimer's disease (AD) has emerged as a serious global problem, and it has been considered as the most common type of dementia. PPAR gamma and beta-secretase 1 (BACE1) are considered as potential targets for Alzheimer's disease management. In the same time, sulfonylureas and sulfonamides have been confirmed to have PPAR gamma agonistic activity. Aiming to obtain new anti-AD agents, thirty-five compounds of sulfonamide and sulfonylurea derivatives having the same essential pharmacophoric features of the reported PPAR gamma agonists have been subjected to virtual screening. Docking studies revealed that five compounds (1, 2, 3, 4, and 5) have promising affinities to PPAR gamma. They were also docked into the binding site of BACE1. In addition, ADMET and physicochemical properties of these compounds were considered. Additionally, these compounds were further evaluated against BACE1 and PPAR gamma. Compound 2 showed IC(50)value of 1.64 mu M against BACE1 and EC(50)value of 0.289 mu M against PPAR gamma.