New Strategies for Designing Scutellarein Derivatives to Combat Alzheimer’s Disease: A Research-Based Medicinal Chemistry Experiment for Undergraduates Majoring in Pharmaceutical Science

Based on the multitarget directed ligand (MTDL) strategy, which has the core advantages and potential value of achieving synergistic regulation of multiple pathological stages of Alzheimer’s disease (AD) through a single molecule, this experiment designed a scutellarein derivative that combines acetylcholinesterase (AChE) inhibition and a H3 receptor (H3R) antagonistic synergistic mechanism and conducted a relevant evaluation to enhance the practical ability of undergraduate students in medicinal chemistry. To achieve this goal, we conducted a 4-week comprehensive medicinal chemistry experiment (8 h per week) in the medicinal chemistry experimental course for third year undergraduate students. This comprehensive experiment covers the sequential stages of drug development, including molecular design, chemical synthesis, structural characterization, biological evaluation, and drug–target molecule docking. The experimental results indicate that the designed target compound has a synergistic effect of AChE inhibition/H3R antagonism, and the molecular docking results between the target compound and the key targets reveal the molecular recognition mechanism between them. Finally, this experiment can enhance students’ understanding and application of multitarget directed ligand strategies in the structural modification of active natural products for the treatment of AD and can strengthen the connection between theoretical knowledge and practical training. This article describes the various processes of this comprehensive experiment as well as the learning outcomes of students in the medicinal chemistry laboratory course.