QSAR studies of antiviral agents using molecular similarity analysis and structure-activity maps

Quantitative structure-activity relationships (QSAR) were developed for nucleoside analogs with anti-HIV activity. These compounds were investigated to determine the correlation of structure and toxicity/activity using molecular similarity analysis and structure-activity maps. A multiple-formula approach was used to perform quantitative molecular similarity analysis (QMSA) and QSAR study. Molecular descriptors such as number of atoms and bonds of a molecule (NAB), maximum common substructure (MaCS), and molecular similarity index (MSI) were used in our structure-activity relationship study. The MaCS of two molecules is defined as the substructure with the greatest NAB value common to both molecules. The MSI of two molecules X and Y is defined as MSI(X,Y) = [MaCS(X,Y)/NAB(X)] x [MaCS(X,Y)/NAB(Y)]. MaCS and MSI quantify the similarity between two molecular structures. Structure-activity maps (structure-toxicity map and structure-antiviral map) and QMSA were used to determine the site and type of modification for reduced toxicity and improved activity of new compounds.