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

Quantitative structure-activity relationships (QSAR) were developed for nuc leoside analogs with anti-HIV activity. These compounds were investigated t o determine the correlation of structure and toxicity/activity using molecu lar similarity analysis and structure-activity maps, A multiple-formula app roach was used to perform quantitative molecular similarity analysis (QMSA) and OSAR study. Molecular descriptors such as number of atoms and bonds of a molecule (NAB), maximum common substructure (MaCS), and molecular simila rity index (MSI) were used in our structure-activity relationship study. Th e MaCS of two molecules is defined as the substructure with the greatest NA B value common to both molecules. The MSI of two molecules X and Y is defin ed as MSI(X,Y) = [MaCS((X,Y))/NAB((X))] x [MaCS((X,Y))/ NAB((Y))]. MaCS and MSI quantify the similarity between two molecular structure. Structure-act ivity maps (structure-toxicity map and structure-antiviral map) and QMSA we re used to determine the sire and type of modification for reduced toxicity and improved activity of new compounds.