Fingerprint-based consensus virtual screening towards structurally new 5-HT(6)R ligands

Bioorg Med Chem Lett. 2015 May 1;25(9):1827-30. doi: 10.1016/j.bmcl.2015.03.049. Epub 2015 Mar 24.

Abstract

Virtual screening towards the search of new 5-HT6R ligands was carried out with three different fingerprints used for molecules representation. Two structurally new compounds were found to be characterized by a significant 5-HT6R activity (Ki of 119 and 670 nM). The compounds do not possess a positive ionizable group in their structures and therefore they belong to the group of atypical, non-basic 5-HT6R ligands. The obtained hits were proved to fit well in the 5-HT6R binding cavity by docking and molecular dynamic simulation experiments. Moreover, an in silico evaluation of the ADMET properties of these compounds predicted their drug-like character.

Keywords: Fingerprint-based consensus; Serotonin receptor 5-HT(6); Support vector machines; Virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cricetulus
  • Drug Evaluation, Preclinical
  • HEK293 Cells
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Receptors, Serotonin / metabolism*

Substances

  • Ligands
  • Receptors, Serotonin
  • serotonin 6 receptor