Structural characteristics of novel symmetrical diaryl derivatives with nitrogenated functions. Requirements for cytotoxic activity

Bioorg Med Chem. 2006 Mar 15;14(6):1942-8. doi: 10.1016/j.bmc.2005.10.041. Epub 2005 Nov 10.

Abstract

In an attempt to discover the essential features that would allow us to explain the differences in cytotoxic activity shown by a series of symmetrical diaryl derivatives with nitrogenated functions, we have studied by molecular modelling techniques the variation in Log P and conformational behaviour, in terms of structural modifications. The Log P data--although they provide few clues concerning the observed variability in activity--suggest that an initial separation of active and inactive compounds is possible based on this parameter. The subsequent study of the conformational behaviour of the compounds, selected according to their Log P values, showed that the active compounds preferentially display an extended conformation and inactive ones are associated with a certain type of folding, with a triangular-type conformation adopted in these cases.

MeSH terms

  • Benzene Derivatives / chemical synthesis*
  • Benzene Derivatives / toxicity*
  • Computer Simulation
  • Crystallography, X-Ray
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Models, Molecular
  • Molecular Conformation
  • Nitrogen / chemistry*
  • Structure-Activity Relationship

Substances

  • Benzene Derivatives
  • Nitrogen