title: A three-dimensional chemical phase pharmacophore mapping, QSAR modelling and electronic feature analysis of benzofuran salicylic acid derivatives as LYP inhibitors.
abstract: 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.
authors.affiliation: a Computer Aided Drug Design and Molecular Modelling Lab, Department of Bioinformatics , Alagappa University , Tamil Nadu , India .
authors.forename: V
authors.initials: V
authors.lastname: Suryanarayanan
authors.forename: S Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: S Kumar
authors.initials: SK
authors.lastname: Tripathi
authors.forename: C
authors.initials: C
authors.lastname: Selvaraj
authors.forename: K Konda
authors.initials: KK
authors.lastname: Reddy
authors.forename: A
authors.initials: A
authors.lastname: Karthiga
mesh_terms: D001572:Benzofurans / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D020156:Salicylic Acid / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D001572:Benzofurans; D004791:Enzyme Inhibitors; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C105430:benzofuran; D020156:Salicylic Acid