Development of Phthalimide-Linked 1,2,3-Triazoles as New Inhibitors of Acetylcholinesterase, Pancreatic Lipase, and Tyrosinase

Abstract

A range of new hybrid 1,2,3-triazole compounds containing a phthalimide ring were synthesized and evaluated for their potential in treating Alzheimer's disease, skin disorders, and obesity health issues. The discovery of tyrosinase inhibitors has gained importance for managing skin pigmentation disorders, pancreatic lipase (PL) inhibitors for controlling obesity, and acetylcholinesterase (AChE) inhibitors for the treatment of Alzheimer's and Parkinson's diseases. To find new and reliable inhibitors of the respective enzymes, the target products (compounds 12-19) were synthesized and characterized by 1H, 13C-NMR, HR-MS, and FT-IR analyses. Enzyme inhibition activities of the novel triazole compounds against tyrosinase, AChE, and PL were evaluated by measuring their IC50 values and comparing them with standard inhibitors, such as kojic acid, tacrine, and orlistat, respectively. Among the synthesized triazoles, compound 15 was found to be the most effective inhibitor of AChE (IC50 = 8.2 +/- 0.41 mu M) and PL (IC50 = 17.8 +/- 0.71 mu M), while compound 17 (IC50 = 15.0 +/- 0.5 mu M) for tyrosinase. Furthermore, antioxidant properties were assessed using ABTS, DPPH, FRAP, and CUPRAC assays. Finally, molecular docking studies explored the molecular interactions with the target enzymes. In vitro and in silico results showed good correlation, suggesting that these hybrid triazoles have promising biological activity and may serve as lead compounds for drug development.