3,5-Diarylpyrazole Derivatives Obtained by Ammonolysis of the Total Flavonoids from Chrysanthemum indicum Extract Show Potential for the Treatment of Alzheimer’s Disease

Four new 3,5-diarylpyrazole analogues (1–4) were isolated from an extract of the flowers of Chrysanthemun indicum using a combination of ammonolysis of the total flavonoid extract and an Aβ aggregation inhibitory activity guided purification procedure. All four compounds (1–4) showed moderate to potent activity against Aβ aggregation with EC₅₀ values of 4.3, 15.8, 1.3, and 2.9 μM, respectively. Moreover, compound 3 showed low cytotoxicity and significant neuroprotective activity against Aβ-induced cytotoxicity in the SH-SY5Y cell line. This report is the first to show that 3,5-diarylpyrazole analogues can inhibit Aβ aggregation and exhibit neuroprotective activity with potential for the treatment of Alzheimer’s disease. Taken together, the method presented here offers an alternative approach to yield bioactive compounds.