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Exploration of nitroimidazoles as radiosensitizers: application of multilayered feature selection approach in QSAR modeling

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Abstract

Radiosensitizers are aimed to augment tumor cell killing by radiation while having much less effect on normal tissues. Nitroimidazoles and related analogues are efficient radiation sensitivity enhancers, and they particularly work on hypoxic tumor cells. In the current study, we have developed two partial least squares (PLS) regression-based two-dimensional quantitative structure-activity relationship (2D-QSAR) models using a novel class of 84 nitroimidazole compounds to understand their radiosensitization effectiveness (pC1.6). Feature selection was done by genetic algorithm along with stepwise regression, while model validation was performed using various stringent validation criteria following the strict rules of OECD guidelines of QSAR validation. The variables included in the models were obtained from Dragon (version 7.0) and simplex representation of molecular structures (SiRMS) (version 4.1.2.270) software. The developed models were robust, externally predictive, and useful tools to predict the radiosensitization effectiveness of nitroimidazole compounds. True external prediction was carried out using a group of six nitroimidazole derivatives and the model reliability was checked using the Prediction Reliability Indicator tool (http://dtclab.webs.com/software-tools). Furthermore, the developed models will give an insight for development of new radiosensitizers with enhanced radiation sensitivity.

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Correspondence to Kunal Roy.

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De, P., Bhattacharyya, D. & Roy, K. Exploration of nitroimidazoles as radiosensitizers: application of multilayered feature selection approach in QSAR modeling. Struct Chem (2020) doi:10.1007/s11224-019-01481-z

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Keywords

  • Radiosensitizers
  • Radiosensitization effectiveness
  • QSAR
  • SiRMS