A Comprehensive QSAR Treatment of the Genotoxicity of Heteroaromatic and Aromatic Amines

Abstract

A quantitative structure-activity relationship with R 2 0X8344 R 0X9135 has been derived from a set of 95 heteroaromatic and aromatic amines to correlate and predict their mutagenic activity. It consists of six descriptors calculated from the molecular structures with quantumchemical methods. The descriptors in the model reveal the importance in mutagenic interactions of heteroaromatic amines of hydrogen bonding, of effects induced by the solvent, and of the size of compound. The model also suggests that the amino group is critical for the reactive site.

The Permeability of an Artificial Membrane for Wide Range of pH in Human Gastrointestinal Tract: Experimental Measurements and Quantitative StructureActivity Relationship

“…BMLR algorithm selects the derived descriptor as second best descriptors into the QSAR model. The correlation improvement cut‐off value52,53 was analyzed and it drops below 0.03 for descriptors after the second descriptors for both square root of correlation coefficient ( R 2 ) and square root of cross‐validated correlation coefficient ( R 2 cv ). Additional descriptors do not contribute to the description of structural variation considerably and therefore, the selected model contains two descriptors: logarithmic octanol‐water partition coefficient (log P ow ) and the new hydrogen bonding surface area descriptor (HBSA DA ).…”

Non-Linear QSAR Treatment of Genotoxicity

“…The best multiple linear model for the description of log R from the Ames test for 95 aromatic and heteroaromatic amines had been obtained as follows [21] where N R denotes the number of rings in the compounds, y is the ypolarizability, HASA, and HDSA are the hydrogen bond acceptor and hydrogen bond donor surface areas [22,23], respectively. The two last descriptors are the maximum total interaction energies for a C -C bond and for a C-N bond in the molecule.…”

The Present Utility and Future Potential for Medicinal Chemistry of QSAR / QSPR with Whole Molecule Descriptors

“…The MLR study resulted in QSAR model that consists of six descriptors, mainly of quantum-chemical origin, which indicate the importance of hydrogen bonding, of effects induced by the solvent, and of the size of compound [130]. The majority of QSAR models on genotoxicity involve log P as determining descriptor of the equation.…”