Computational Toxicology

Chapter 5Pharmacophore Models for Toxicology Prediction

Daniela Schuster

Institute of Pharmacy/Pharmaceutical Chemistry, University of Innsbruck, Innsbruck, Austria

Chapter Menu

1. Introduction
2. Antitarget Screening
3. Prediction of Liver Toxicity
4. Prediction of Cardiovascular Toxicity
5. Prediction of Central Nervous System (CNS) Toxicity
6. Prediction of Endocrine Disruption
7. Prediction of ADME
8. General Remarks on the Limits and Future Perspectives for Employing Pharmacophore Models in Toxicological Studies

5.1 Introduction

For the virtual screening-based discovery of bioactive compounds, pharmacophore models have been successfully used for three decades now. However, the concept of a pharmacophore, then also called toxicophore or haptophore, was first defined by Ehrlich [1] and later redefined by Schueler [2, 3]. It is defined by the IUPAC as “… the ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target structure and to trigger (or to block) its biological response. A pharmacophore does not represent a real molecule or a real association of functional groups, but a purely abstract concept that accounts for the common molecular interaction capacities of a group of compounds toward their target structure.” [4]. Pharmacophore models consist of so-called chemical features that represent specific molecular interaction types such as hydrogen bonds, aromatic interactions, charged centers, metal interactions, ...