QSAR modeling on benzo[c]phenanthridine analogues as topoisomerase I inhibitors and anti-cancer agents

Molecules. 2012 May 11;17(5):5690-712. doi: 10.3390/molecules17055690.


Benzo[c]phenanthridine (BCP) derivatives were identified as topoisomerase I (TOP-I) targeting agents with pronounced antitumor activity. In this study, hologram-QSAR, 2D-QSAR and 3D-QSAR models were developed for BCPs on topoisomerase I inbibitory activity and cytotoxicity against seven tumor cell lines including RPMI8402, CPT-K5, P388, CPT45, KB3-1, KBV-1and KBH5.0. The hologram, 2D, and 3D-QSAR models were obtained with the square of correlation coefficient R² = 0.58-0.77, the square of the crossvalidation coefficient q² = 0.41-0.60 as well as the external set's square of predictive correlation coefficient r² = 0.5-0.80. Moreover, the assessment method based on reliability test with confidence level of 95% was used to validate the predictive power of QSAR models and to prevent over-fitting phenomenon of classical QSAR models. Our QSAR model could be applied to design new analogues of BCPs with higher antitumor and topoisomerase I inhibitory activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA Topoisomerases, Type I / chemistry*
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Phenanthridines / chemical synthesis*
  • Phenanthridines / pharmacology
  • Quantitative Structure-Activity Relationship*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Topoisomerase I Inhibitors / chemical synthesis*
  • Topoisomerase I Inhibitors / pharmacology


  • Antineoplastic Agents
  • Phenanthridines
  • Topoisomerase I Inhibitors
  • DNA Topoisomerases, Type I
  • TOP1 protein, human