Pieroni E., Kumar A., Pisu M., Genna V., Concas A., Cao G., 2013, Combination of Classical and Molecular Modeling Approaches to Investigate the Effect of Antipsychotic Drugs on Cell Proliferation Kinetics, Chemical Engineering Transactions, 32, 787-792.
A novel approach to investigate the effect of drugs on cell proliferation is proposed and addressed in a case study concerning Human Umbilical Vein Endothelial Cells (HUVECs) in vitro cultivation in the presence of an antipsychotic drug, i.e. Clozapine. A mathematical model based on mass structured population balance (PB) has been proposed to simulate experimental data concerning cell count and its size distribution, as well as the nutrient (glucose) concentration, as a function of cultivation time. Molecular modeling studies have been in parallel performed to investigate the drug interaction with serotonin receptor (5-HT2AR) and the dopamine one (D2R). In particular, by combining classical and molecular modeling approaches, it is shown that it is possible to quantitatively estimate one of the most relevant receptor parameter (i.e. the allosteric constant related to the equilibrium between active and inactive receptor state). Results show also that Clozapine plays a role as an inverse agonist with serotonin and dopamine receptors providing a contribution to the cell growth inhibition mechanism. The obtained results are in good agreement with the known pharmaceutical actions of the drug and show the viability of the proposed methodology.
