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Toxicophore exploration as a screening technology for drug design and discovery: techniques, scope and limitations

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Abstract

Toxicity is a common drawback of newly designed chemotherapeutic agents. With the exception of pharmacophore-induced toxicity (lack of selectivity at higher concentrations of a drug), the toxicity due to chemotherapeutic agents is based on the toxicophore moiety present in the drug. To date, methodologies implemented to determine toxicophores may be broadly classified into biological, bioanalytical and computational approaches. The biological approach involves analysis of bioactivated metabolites, whereas the computational approach involves a QSAR-based method, mapping techniques, an inverse docking technique and a few toxicophore identification/estimation tools. Being one of the major steps in drug discovery process, toxicophore identification has proven to be an essential screening step in drug design and development. The paper is first of its kind, attempting to cover and compare different methodologies employed in predicting and determining toxicophores with an emphasis on their scope and limitations. Such information may prove vital in the appropriate selection of methodology and can be used as screening technology by researchers to discover the toxicophoric potentials of their designed and synthesized moieties. Additionally, it can be utilized in the manipulation of molecules containing toxicophores in such a manner that their toxicities might be eliminated or removed.

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Acknowledgments

R.K. and M.C. thank Department of Science and Technology, New Delhi, for the financial assistance (F. No. SR/FT/CS-71/2011). Support from Research Seed Money (RSM) from CUPB is also acknowledged. R.K. also thanks University Grant Commission-Major Grant (F. No. 42-676/2013(SR).

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  1. Laboratory for Drug Design and Synthesis, Centre for Pharmaceutical Sciences and Natural Products, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151 001, India

    Pankaj Kumar Singh, Arvind Negi, Monika Chauhan & Raj Kumar

  2. Centre for Computational Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151 001, India

    Pawan Kumar Gupta

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  1. Pankaj Kumar Singh
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Singh, P.K., Negi, A., Gupta, P.K. et al. Toxicophore exploration as a screening technology for drug design and discovery: techniques, scope and limitations. Arch Toxicol 90, 1785–1802 (2016). https://doi.org/10.1007/s00204-015-1587-5

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