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

A new analysis of the quantitative structure-activity relationship (QSAR) o f the antitumor activity of anilinoacridines against L1210 leukemia in mice and mouse toxicity is reported. QSAR have also been derived for the inhibi tory 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 substit uents tin general negative coefficients with the Hammett parameter sigma(+) ) throughout the various systems and the complete lack of hydrophobic inter actions from DNA to cells to mice. The presence of steric terms suggests th at a protein receptor is involved. The study shows that QSAR has an importa nt role to play in improving the efficiency in the design of bioactive comp ounds and that care must be taken in the design of a set of congeners so th at the necessary parameters are available to do the QSAR analysis. Our stud y illustrates the value of comparative QSAR in generalizing our understandi ng of chemical-biological interactions. (C) 1998 Elsevier Science Ireland L td. All rights reserved.