A three-dimensional chemical phase pharmacophore mapping, QSAR modelling and electronic feature analysis of benzofuran salicylic acid derivatives as LYP inhibitors
| Autor: | Chandrabose Selvaraj, Arumugasamy Karthiga, S Kumar Singh, Venkatesan Suryanarayanan, K Konda Reddy, S Kumar Tripathi |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Quantitative structure–activity relationship Hydrogen bond Stereochemistry Static Electricity Quantitative Structure-Activity Relationship Reproducibility of Results Bioengineering Hydrogen Bonding Protein Tyrosine Phosphatase Non-Receptor Type 22 General Medicine Protein tyrosine phosphatase Ring (chemistry) chemistry.chemical_compound chemistry Drug Discovery Molecular Medicine Humans Density functional theory Benzofuran Pharmacophore Enzyme Inhibitors Salicylic Acid HOMO/LUMO Benzofurans |
| Zdroj: | SAR and QSAR in environmental research. 24(12) |
| ISSN: | 1029-046X |
| Popis: | Lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, has a critical negative regulatory role in T-cell antigen receptor (TCR) and emerged as a promising drug target for human autoimmune diseases. A five-point pharmacophore with two hydrogen bond acceptors, one hydrogen bond donor and two aromatic ring features was generated for a series of benzofuran salicylic acid derivatives as LYP inhibitors in order to elucidate their anti-autoimmune activity. The generated pharmacophore yielded a significant 3D-QSAR model with r(2) of 0.9146 for a training set of 27 compounds. The model also showed excellent predictive power with Q(2) of 0.7068 for a test set of eight compounds. The investigation of the 3D-QSAR model has revealed the structural insights which could lead to more potent analogues. The most active and inactive compounds were further subjected to electronic structure analysis using density functional theory (DFT) at B3LYP/3-21(∗)G level to support the 3D-QSAR predictions. The results obtained from this study are expected to be useful in the proficient design and development of benzofuran salicylic acid derivatives as inhibitors of LYP. |
| Databáze: | OpenAIRE |
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