title: Synthesis, bioactivity, 3D-QSAR studies of novel dibenzofuran derivatives as PTP-MEG2 inhibitors.
abstract: PTP-MEG2 plays a critical role in the diverse cell signalling processes, so targeting PTP-MEG2 is a promising strategy for various human diseases treatments. In this study, a series of novel dibenzofuran derivatives was synthesized and assayed for their PTP-MEG2 inhibitory activities. 10a with highest inhibitory activity (320 nM) exhibited significant selectivity for PTP-MEG2 over its close homolog SHP2, CDC25 (IC50 > 50 μM). By means of the powerful ''HipHop'' technique, a 3D-QSAR study was carried out to explore structure activity relationship of these molecules. The generated pharmacophore model revealed that the one RA, three Hyd, and two HBA features play an important role in binding to the active site of the target protein-PTP-MEG2. Docking simulation study indicated that 10a achieved its potency and specificity for PTP-MEG2 by targeting unique nearby peripheral binding pockets and the active site. The absorption, distribution, metabolism and excretion (ADME) predictions showed that the 11 compounds hold high potential to be novel lead compounds for targeting PTP-MEG2. Our findings here can provide a new strategy or useful insights for designing the effective PTP-MEG2 inhibitors.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.|Eye Hospital, Tianjin Medical University, School of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, China.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Wei
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
authors.forename: Yu-Ze
authors.initials: YZ
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Jin
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
authors.forename: Hong-Lian
authors.initials: HL
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
authors.forename: Xian-Chao
authors.initials: XC
authors.lastname: Cheng
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
authors.forename: Run-Ling
authors.initials: RL
authors.lastname: Wang
mesh_terms: D000072318:Dibenzofurans / Q000138:chemical synthesis* / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000072318:Dibenzofurans; D004791:Enzyme Inhibitors; C447615:PTPN9 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor
keywords: 3D-QSAR; PTP-MEG2; dibenzofuran; docking; synthesis