From molecular graphs to drugs. A review on the use of topological indices in drug design and discovery

Abstract

A review on the use of topological indices (TIs) in the process of drug design and development is presented on the basis of the most recent advances in this field. The first part of this work is focussed on introducing the definitions of terms used in drug design and discovery, graph-theoretical chemistry as well as topological indices. The second part of the review discusses the use of topological indices in the lead discovery and optimization processes, including similarity/dissimilarity studies, rational combinatorial library design, QSAR, the issue of 2D versus 3D QSAR, as well as the use of novel chemometric techniques, such as artificial neural networks, genetic algorithms and partial least squares in combination with TIs. Recent advances on the definition of TIs accounting for three dimensional molecular features (topographic indices) and molecular chirality are also presented.