Pharmacophore modeling and 3D QSAR analysis of isothiazolidinedione derivatives as PTP1B inhibitors

Girdhar Singh Deora, Prashant Joshi, Vandana Rathore, K. Lalith Kumar, Renu Ohlyan, Ajit Kandale

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10 Citations (Scopus)

Abstract

The article describes the development of a robust pharmacophore model and investigation of structure activity relationship analysis of 56 isothiazolidinedione derivatives reported as PTP1B inhibitors. A six-point pharmacophore model consisting of four aromatic rings (R), one hydrogen bond donor (D) and one hydrogen bond acceptor (A) with discrete geometries as pharmacophoric features was developed and the generated pharmacophore model was used to derive a predictive 3D QSAR model for the studied dataset. The obtained 3D QSAR model has an excellent correlation coefficient value (r 2 = 0.98) along with good statistical significance as shown by a high Fisher ratio (F = 428.60). The model also exhibits good predictive power confirmed by the high value of cross-validated correlation coefficient (q 2 = 0.62). The QSAR model suggests that hydrophobic aromatic character is crucial for the PTP1B inhibitory activity at the R-15 site. 

Original languageEnglish
Pages (from-to)3478-3484
Number of pages7
JournalMedicinal Chemistry Research
Volume22
Issue number7
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

Keywords

  • 3D QSAR
  • Isothiazolidinedione derivatives
  • Pharmacophore modeling
  • PHASE
  • PTP1B inhibitors

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