TY - JOUR T1 - Chemoinformatics Profiling of the Chromone Nucleus as a MAO-B/A2AAR Dual Binding Scaffold. AU - Cruz-Monteagudo,Maykel, AU - Borges,Fernanda, AU - Cordeiro,M Natalia D S, AU - Helguera,Aliuska Morales, AU - Tejera,Eduardo, AU - Paz-Y-Mino,Cesar, AU - Sanchez-Rodriguez,Aminael, AU - Perera-Sardina,Yunier, AU - Perez-Castillo,Yunierkis, PY - 2015/11/26/received PY - 2016/03/14/revised PY - 2016/11/03/accepted PY - 2017/1/18/pubmed PY - 2018/7/17/medline PY - 2017/1/18/entrez KW - A2A adenosine receptor KW - chemoinformatics KW - chromones KW - dual-target binder KW - monoamine oxidase B KW - parkinson's disease. SP - 1117 EP - 1135 JF - Current neuropharmacology JO - Curr Neuropharmacol VL - 15 IS - 8 N2 - BACKGROUND: In the context of the current drug discovery efforts to find disease modifying therapies for Parkinson's disease (PD) the current single target strategy has proved inefficient. Consequently, the search for multi-potent agents is attracting more and more attention due to the multiple pathogenetic factors implicated in PD. Multiple evidences points to the dual inhibition of the monoamine oxidase B (MAO-B), as well as adenosine A2A receptor (A2AAR) blockade, as a promising approach to prevent the neurodegeneration involved in PD. Currently, only two chemical scaffolds has been proposed as potential dual MAO-B inhibitors/A2AAR antagonists (caffeine derivatives and benzothiazinones). METHODS: In this study, we conduct a series of chemoinformatics analysis in order to evaluate and advance the potential of the chromone nucleus as a MAO-B/A2AAR dual binding scaffold. RESULTS: The information provided by SAR data mining analysis based on network similarity graphs and molecular docking studies support the suitability of the chromone nucleus as a potential MAOB/ A2AAR dual binding scaffold. Additionally, a virtual screening tool based on a group fusion similarity search approach was developed for the prioritization of potential MAO-B/A2AAR dual binder candidates. Among several data fusion schemes evaluated, the MEAN-SIM and MIN-RANK GFSS approaches demonstrated to be efficient virtual screening tools. Then, a combinatorial library potentially enriched with MAO-B/A2AAR dual binding chromone derivatives was assembled and sorted by using the MIN-RANK and then the MEAN-SIM GFSS VS approaches. CONCLUSION: The information and tools provided in this work represent valuable decision making elements in the search of novel chromone derivatives with a favorable dual binding profile as MAOB inhibitors and A2AAR antagonists with the potential to act as a disease-modifying therapeutic for Parkinson's disease. SN - 1875-6190 UR - https://www.unboundmedicine.com/medline/citation/28093976/Chemoinformatics_Profiling_of_the_Chromone_Nucleus_as_a_MAO_B/A2AAR_Dual_Binding_Scaffold_ DB - PRIME DP - Unbound Medicine ER -