Quantitative structure-activity relationships (QSAR) for 9-anilinoacridines: a comparative analysis

Chem Biol Interact. 1998 Nov 27;116(3):157-80. doi: 10.1016/s0009-2797(98)00085-4.

Abstract

A new analysis of the quantitative structure-activity relationship (QSAR) of the antitumor activity of anilinoacridines against L1210 leukemia in mice and mouse toxicity is reported. QSAR have also been derived for the inhibitory activity of the anilinoacridines with tumor cells and their binding to DNA. These results are compared with reactivity with simple nucleophiles. The comparative analysis shows the importance of electron releasing substituents (in general negative coefficients with the Hammett parameter sigma+) throughout the various systems and the complete lack of hydrophobic interactions from DNA to cells to mice. The presence of steric terms suggests that a protein receptor is involved. The study shows that QSAR has an important role to play in improving the efficiency in the design of bioactive compounds and that care must be taken in the design of a set of congeners so that the necessary parameters are available to do the QSAR analysis. Our study illustrates the value of comparative QSAR in generalizing our understanding of chemical-biological interactions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amsacrine / analogs & derivatives*
  • Amsacrine / chemistry
  • Amsacrine / pharmacokinetics
  • Amsacrine / pharmacology
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Drug Design
  • Kinetics
  • Leukemia L1210 / drug therapy
  • Leukemia L1210 / metabolism
  • Mice
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Amsacrine
  • 9-anilinoacridine