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Validation of Formylchromane Derivatives as Protein Tyrosine Phosphatase 1 B Inhibitors by Pharmacophore Modeling, Atom‐Based 3 D ‐ QSAR and Docking Studies
Author(s) -
Malla Priyanka,
Kumar Rajnish,
Kumar Manoj
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12135
Subject(s) - pharmacophore , chemistry , stereochemistry , quantitative structure–activity relationship , active site , moiety , docking (animal) , molecular descriptor , molecular dynamics , hydrogen bond , protein tyrosine phosphatase , enzyme , biochemistry , molecule , computational chemistry , organic chemistry , medicine , nursing
Formylchromane derivatives were reported to possess irreversible and selective inhibition on human protein tyrosine phosphatase 1 B ( PTP 1 B ). Inhibition of PTP 1 B is a molecular level legitimate approach for the management of type 2 diabetes mellitus ( T 2 DM ). 3 D ‐ QSAR studies were performed on a series of formylchromane derivatives using partial least square ( PLS ) analysis for correlating molecular architecture of the analogs with their PTP 1 B inhibitory activity. A five‐point pharmacophore hypothesis with three hydrogen bond acceptors ( A ) and two aromatic rings ( R ) as pharmacophoric features was developed using phase module of Schrödinger suite. The hypothesis AAARR .160 was considered as best hypothesis in this study characterized by survival score (3.483), the best cross‐validated r 2 ( Q 2 ) (0.774), regression coefficient (0.960), Pearson‐R (0.891), and F value (100.3). The results of hypothesis AAARR .160 complimented very closely to interactions witnessed in active site of the ligand‐bound complex. The molecular docking simulations into PTP 1 B active site also highlighted that biphenyl moiety favorably interacted with amino acid residues lining the lipophilic pocket, and provided hydrophobic interactions with receptor active site. These observations might be useful for further development and optimization of new chemical entities as potential PTP 1 B inhibitors prior to its synthesis.