Pharmacophoric sites of anticancer metal complexes located using quantum topological atomic descriptors

Abstract

We present a new set of topological atomic descriptors (TAD) to identify pharmacophoricsites, using the anti-tumoral activities of metal copper (II) complexes. To this end, multiple linearregression-based models were built using TAD. These descriptors are related with the atomic electronicpopulation, localization and delocalization, dipolar moment and quadrupole moment, and describe theway in which the atoms donate, accept or share electron density and how the electron density ispolarized within an atomic domain. The regression models were built to reproduce the antiproliferativeactivity on two tumor human cells lines. Usually, the activity analysis of a metal complex focusses on themetal center features, but the ligands have a definitive role on the molecular recognition of the com-plexes by the biomolecules. In this case, the best models selected are those involving the changes of thedelocalization and dipole moments of atoms within the CeN bonds of the ligands. These changescorrelate with the antiproliferative activity and, thus, it allows to identify the CeN bonds as the phar-macophoric site of the copper complexes. These bonds are determinant for the recognition site of coppercomplexes by DNA backbone, as found in a previous molecular dynamics study performed by our group.