A Rational Approach to the Optimal Design of Drugs.

Recent advances in the rational design of drug molecules based on a graph-theoretical approach are briefly reviewed. Graph theory has not been widely recognized to date as an effective alternative to the empirical procedures currently prevailing in the development of new drugs. Moreover, the problems confronting researchers in this field are daunting in their great complexity. We advocate here a novel yet simple mathematical formalism which opens up a promising new avenue of research. After outlining the fundamental premises of our method, we exemplify it by discussing the characterization, comparison, and quantification of similarity among individual molecules. It is indicated how the essential bioactive component in molecules of compounds displaying similar pharmacological behavior may be identified. We conclude by describing the pharmacological classification of 18 compounds, all of which are structurally similar but which exhibit several differing types of bioactivity.