Design, synthesis of novel azolyl flavonoids and their protein tyrosine Phosphatase-1B inhibitory activities. 2018

Ling Zhang, and Yu Ge, and Hao Ming Song, and Qing Ming Wang, and Cheng-He Zhou
School of Pharmacy, Yancheng Teachers' University, Yancheng, Jiangsu 224051, People's Republic of China. Electronic address: zhangl@yctu.edu.cn.

A series of azolyl flavonoids were synthesized and characterized by NMR, IR, MS and HRMS spectra. All the newly prepared compounds were screened for their potential protein tyrosine phosphatase inhibitory activities. Bioactive assay manifested that most of the azolyl flavonoids exhibited good protein phosphatase 1B (PTP1B) inhibitory activities. Especially, triazolyl flavonoid 6a displayed the best inhibitory activity (IC50 = 1.6 μM) with 9.9-fold selectivity for PTP1B over the closely related T-cell protein tyrosine phosphatase (TCPTP). Cell viability assays indicated 6a has lower cytotoxicity. Molecular modeling and dynamics studies revealed the reason of selectivity for PTP1B over TCPTP. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D011789 Quantum Theory The theory that the radiation and absorption of energy take place in definite quantities called quanta (E) which vary in size and are defined by the equation E Quantum Theories,Theories, Quantum,Theory, Quantum
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005419 Flavonoids A group of phenyl benzopyrans named for having structures like FLAVONES. 2-Phenyl-Benzopyran,2-Phenyl-Chromene,Bioflavonoid,Bioflavonoids,Flavonoid,2-Phenyl-Benzopyrans,2-Phenyl-Chromenes,2 Phenyl Benzopyran,2 Phenyl Benzopyrans,2 Phenyl Chromene,2 Phenyl Chromenes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D054562 Protein Tyrosine Phosphatase, Non-Receptor Type 1 A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM. PTPase 1B,PTPase HA2,Protein Tyrosine Phosphatase 1B,Protein-Tyrosine Phosphatase HA2,Protein Tyrosine Phosphatase HA2,Protein Tyrosine Phosphatase, Non Receptor Type 1

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