In Silico Analysis Used to Estimate Active Compounds of Phthalazinones and the Potential Pharmacological Mechanism in Alzheimer's Disease Treatment

Abstract

Alzheimer's disease (AD) is prevalent among the aged and new drugs for AD are always in necessary. In this study, network pharmacology and molecular docking were adopted to bioactivity screening as well as pharmacological mechanism investigation, of phthalazinones. Those phthalazinones with certain structures and physical properties were screened out by PubChem database. And molecular docking was used to explore the potential activity of these phthalazinones as drugs for AD treatment. Secondly, network pharmacology analysis of phthalazinones and the drugs approved for AD were employed, including targets prediction, gene enrichment analysis and network analysis. Five compounds (PubChem CID: 137700766, 69619707,137700767, 137700768, 9827600) were recognized and enjoyed lower binding energy. There were 57 targets recognized as common targets that adopted to network construction. Totally 15 approved drugs with clear indications for AD were figured out, with 57 associated targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that phthalazinone derivatives and drugs for AD shared the same essential pathway (neuroactive ligand-receptor interaction) with associated targets. In silico analysis suggested that these phthalazinones are potential to be effective for AD treatment by regulating neuroactive ligand-receptor interaction pathway, calcium signaling pathway, and other pathways.