Structure-cytotoxicity relationships for a series of HEPT derivatives

J Mol Model. 2002 Jan;8(1):1-7. doi: 10.1007/s00894-001-0054-9.

Abstract

Structure-cytotoxicity relationships were studied for a series of 90 HEPT derivatives by means of multiple linear regression (MLR) and artificial neural network (ANN) techniques. The values of log(1/CC50) (CC50=cytotoxic dose of compound required to reduce the proliferation of normal uninfected MT-4 cells by 50%) of the studied compounds were correlated with the descriptors encoding the chemical structures. Using the pertinent descriptors revealed by the regression analysis, a correlation coefficient of 0.935 ( s=0.149) for the training set ( n=81) was obtained for the ANN model with a 5-6-1 configuration. The results obtained from this study indicate that the cytotoxicity of HEPT derivatives is strongly dependent on hydrophobic factors, mainly log P(R1), and dependent on the steric factors, especially SigmaMW(R3+R4). Comparison of the descriptors' contribution obtained in MLR and ANN analysis shows that the contribution of some of the descriptors to cytotoxicity may be non-linear.

MeSH terms

  • Animals
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / toxicity*
  • Cell Line
  • Cell Survival / drug effects
  • Linear Models
  • Neural Networks, Computer
  • Reverse Transcriptase Inhibitors / chemistry*
  • Reverse Transcriptase Inhibitors / toxicity*
  • Structure-Activity Relationship
  • Thymine / analogs & derivatives*
  • Thymine / chemistry*
  • Thymine / toxicity*

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • 1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine
  • Thymine