关键词: 有机化学, 组合化学, 虚拟筛选, 药物合成, 乙酰胆碱酯酶

Abstract: The advent of combinatorial chemistry has revolutionized the rapid synthesis of diverse organic compounds, serving as a pivotal strategy for translating organic chemistry into drug development applications. However, implementation in organic chemistry laboratory education remains challenging due to equipment limitations and constrained instructional time. Guided by combinatorial chemistry principles, we designed and constructed a virtual compound library comprising 4 core scaffolds and 1,836 molecules. Using Sybyl-based virtual screening technology, we identified compound 4-1-8-7-6 as both synthetically accessible and exhibiting the strongest binding affinity for acetylcholinesterase. Subsequent synthesis and biological evaluation demonstrated that 4-1-8-7-6 outperformed the clinical drug tacrine in activity, validating our virtual screening approach. This study successfully simulated the complete combinatorial chemistry and drug screening workflow with minimal cost, innovatively integrating these techniques into organic chemistry laboratory instruction. This interdisciplinary experimental design, combining virtual and practical methodologies, effectively enhances students’ innovative thinking and practical skills, thereby fostering the development of versatile, well-rounded scientific professionals.

Key words: Organic chemistry, Combinatorial chemistry, Virtual screening , Drug synthesis, Acetylcholinesterase