An approach to QSAR of 16-substituted pregnenolones as microsomal enzyme inducers

Eur J Drug Metab Pharmacokinet. Jan-Mar 1996;21(1):7-11. doi: 10.1007/BF03190271.


In this study, we attempt to correlate quantitatively the structure of eight 16-substituted pregnenolones with microsomal enzyme inducing activity. We also performed some electrostatic potential calculations to get further insight into the properties of these substituents. It was found that pregnenolone-16 alpha-carbonitrile is the most active steroidal inducer among the pregnenolone derivatives tested. The receptor-inducer interaction is facilitated by a favourable electronic effect of the 16 alpha-substituents. The orientation of the electronegative area at position 16 seems to influence activity. Lipophilic and volume effects of the 16 alpha-substituents do not seem to be important for microsomal enzyme induction. However, substituent length has some influence on drug metabolising enzyme activity, probably interfering with receptor-inducer interactions.

MeSH terms

  • Animals
  • Enzyme Induction
  • Female
  • In Vitro Techniques
  • Microsomes, Liver / enzymology*
  • Microsomes, Liver / metabolism
  • Pregnenolone Carbonitrile / chemistry
  • Pregnenolone Carbonitrile / metabolism*
  • Rats
  • Static Electricity
  • Structure-Activity Relationship
  • Substrate Specificity


  • Pregnenolone Carbonitrile