Molecular Shape Descriptors: Applications to Structure-Activity Studies

Abstract

Shape is a very important molecular feature for describing ligand molecules interacting with receptor, and other various complex chemical and biological processes. During the last years, there is a strong interest in developing several molecular shape descriptors. In this chapter we present our attempts for deriving van der Waals (vdW) shape molecular descriptors from two size molecular descriptors – the molecular vdW volume (V^W) and the molecular vdW surface (S^W). The ovality Θ _iD , i = 1,2,3 descriptors measure the deviation of the shape of a molecule from a spherical form in one-, two-, and three dimensions, respectively, whilst the {δ,G} molecular shape parameters take into consideration the cylindrical shape of a molecule or substituent. The application of these molecular descriptors in the study of the toxicity of a series of aliphatic amines on the protozoan ciliate Tetrahymena pyriformis (Θ _iD ) and for the correlation of rate constants of bimolecular nucleophilic substitution, acid-catalyzed hydrolysis of esters and esterification reactions (δ) is also reported in this chapter. The MTD (minimal topologic difference) method allows a receptor site mapping in the frame of a series of bioactive compounds. The MVD (minimal volume difference) method is an improved variant of the MTD method, which takes into account the 3D extension of a molecule. These methods are described here in some detail. The results obtained in the study of anti-carcinogenic activity of some retinoids and in the inhibition of carbonic-anhydrase (CA) by a series of sulfonamides are also presented in this chapter.