Journal of Computer-Aided Molecular Design

, Volume 15, Issue 3, pp 195–202 | Cite as

A comparative molecular field analysis of cytochrome P450 2A5 and 2A6 inhibitors

  • Antti Poso
  • Jukka Gynther
  • Risto Juvonen
Article

Abstract

Structure-activity relationships of 23 P450 2A5 and 2A6 inhibitors were analysed using the CoMFA [1] and GOLPE/GRID with smart region definition (SRD) [2]. The predictive power of the resulting models was validated using five compounds not belonging to the model set. All models have high internal and external predictive power and resulting 3D-QSAR models are supporting each other. Both Sybyl and GOLPE highlight properties near lactone moiety to be important for 2A5 and 2A6 inhibition. Another important feature for pIC50 was the size of the substituent in the 7-positon of coumarin. The models suggest that the 2A5 binding site is larger that that of 2A6 due to larger steric regions in the CoMFA coefficient maps and corresponding GOLPE maps. In addition, the maps reveal that 2A6 disfavours negative charge near the lactone moiety of coumarin.

Comparative molecular field analysis Cytochrome P450 GOLPE GRID smart region definition 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Antti Poso
    • 1
  • Jukka Gynther
    • 1
  • Risto Juvonen
    • 2
  1. 1.Department of Pharmaceutical ChemistryUniversity of KuopioKuopioFinland
  2. 2.Department of Pharmacology and ToxicologyUniversity of KuopioKuopioFinland

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