A 3D-QSAR of N-substituted 4-amino3-3-dialkyl-2(3H)-furanoneGABA A receptor modulators based on receptor surface analysis

Savita Bhutoria, Prasenjit K. Mukherjee, Sandeep Chhabra, Nanda Ghoshal

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

A hypothetical receptor surface model has been generated for an allosteric receptor site, "lactone site", on the GABA A receptor using a set of N-substituted 4-amino-3, 3-dialkyl-2 (3H)-furanone GABA A receptor modulators (I). The activity data of each of the molecules was used as a weight in building of receptor surface. The study produced reasonably good predictive model with good conventional and cross-validated r 2 with leave-two-out method (0.998 and 0.943 respectively) in the training set and also in external data set validation (r 2 pred =0.960). Most of the points selected for QSAR to conduct RSA are in the vicinity of the groups in position 3 and 4 and not in the vicinity of carbonyl group and oxygen atom region, predicted as favourable site for binding of molecules. These findings and the lack of direct correlation between interaction energy and biological activity led to infer that the compounds may function following "Message-Address" concept.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalLetters in Drug Design and Discovery
Volume3
Issue number1
DOIs
StatePublished - Feb 1 2006

Keywords

  • 3D-QSAR
  • Anticonvulsant activity
  • GABA receptor
  • RSA

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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