Study on the Pharmacological Mechanism of Phthalazinone Derivatives as Potential Drugs for Alzheimer’s Disease Treatment by Network Pharmacology Analysis and Molecular Docking

Abstract Objective: To screen the bioactivity of phthalazinone derivatives for AD treatment and investigate the potential pharmacological mechanism, the network pharmacology analysis and molecular docking were adopted in this study.Methods: Those phthalazinone derivatives with certain structures and physical properties were screened out by Pubchem database in this study. Besides, to explore the potential activity of these phthalazinone derivatives as drugs for AD treatment, network pharmacology study was employed, including targets prediction, gene enrichment analysis and network analysis. Network analysis of AD approved drugs and molecular docking studies were also adopted to further investigate drug-likeness of phthalazinone derivatives for AD treatment.Results: Five compounds and 57 common targets were recognized and adopted to the construction of compounds-targets network. 15 approved drugs with clear indication for AD were figured out, with 57 associated targets that originated from Homo sapiens. The KEGG enrichment analysis showed that phthalazinone derivatives and approved drugs shared the same essential pathway (neuroactive ligand-receptor interaction) and other important pathways with associated targets. The result of molecular docking indicated that these phthalazinone derivatives could interact with essential targets stably.Conclusion: In silico analysis suggested that these derivatives are probable to be effective for the treatment of AD by interacting with the essential targets and initiating ATP binding, signal transduction, finally regulating neuroactive ligand-receptor interaction pathway、calcium signaling pathway , and so on.