Hydrophobicity versus electrophilicity: A new protocol toward quantitative structure-toxicity relationship (original) (raw)

Chemical Biology & Drug Design

Quantitative structure-activity relationship (QSAR) aims at establishing a relationship between the molecular structure and the various behavioral characteristics of chemical compounds. QSARs represent predictive models based on the application of statistical tools which construct a mathematical equation for a set of homologous molecules for their specific biological behavior (activity/property/toxicity) using information about their chemical structure in terms of molecular descriptors (Roy, Kar, & Das, 2015). QSAR models primarily focus on their application in the reduction in use of experimental animals (Commission of the European Communities, 2001) as done in conventional toxicological testing. These methods are also used in grouping and regulation of existing chemical compounds (e.g., REACH legislation; Worth et al., 2007). QSAR was brought into light in 1962 when Hansch, Maloney, Fujita, & Muir (1962) published a paper showing a correlation between biological activity and n-octanol/water partition coefficient. A wide range of descriptors, such as thermodynamic potentials, quantum chemical and electronic energy descriptors, topology, shape, and hydrophobicity, have been used in the development of different QSARs (Karelson, Lobanov, & Katritzky, 1996). QSAR studies in biochemistry mainly use quantum chemical descriptors such as polarizabilities, dipole moments, charges, orbital energies, and frontier orbital densities to predict different biological activities (