Exploring QSARs with Extended Topochemical Atom (ETA) Indices for Modeling Chemical and Drug Toxicity

Kunal      Roy; Gopinath      Ghosh

doi:10.2174/138161210792389270

Abstract

Development of quantitative structure-activity relationships (QSARs) and quantitative structure-property relationships (QSPRs) has been practiced for prediction of various toxicities and other relevant properties of chemicals including drug candidates to minimize animal testing, cost and time associated with risk assessment and management processes. This communication reviews published reports of QSARs/QSPRs with Extended Topochemical Atom (ETA) indices for modeling chemical and drug induced toxicities and some physicochemical properties relevant to such toxicities. In each study, ETA models have been compared to those developed using various non-ETA models and it was found that the quality of the QSARs involving ETA parameters were comparable to those involving non-ETA parameters. ETA descriptors were also found to increase statistical quality of the models involving non-ETA parameters when used in combination. On the basis of the reported studies, it can be concluded that the ETA descriptors are sufficiently rich in chemical information to encode the structural features contributing to the toxicities and these indices may be used in combination with other topological and physicochemical descriptors for development of predictive QSAR models. Such models may be used for virtual screening and in silico prediction of toxicities, and if appropriately used, these may be proved helpful for regulatory decision support and decision making processes.

Keywords: QSAR, QSPR, QSTR, ETA, TAU, VEM, Toxicity, Extended Topochemical Atom (ETA), Drug Toxicity, Adverse Drug Reactions, ETA Scheme, Nonspecific Toxicity, Acute NSAID Cytotoxicity, Non-Ionic Organic Compounds, Principal component regression analysis, Genetic partial least squares, Multiple linear regression, Topochemically arrived unique, Partial least squares, Bioconcentration Factors