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Molecular Design of Environment-Friendly PAE Derivatives Based on 3D-QSAR Assisted with a Comprehensive Evaluation Method Combining Toxicity and Estrogen Activities

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Abstract

In this paper, a phthalic acid ester (PAE) three-dimensional quantitative structure-activity relationship (3D-QSAR) model with a double activity (toxicity and estrogenic activities) combination was established using a comprehensive evaluation method, in which the database of the combined activities consisted of 17 and 13 employed in the training sets and test sets, respectively. Ditridecyl phthalate (DTDP) derivatives with low-toxicity and estrogen combined activities were designed with DTDP as the target molecule. Four environmentally friendly DTDP derivatives were screened out by evaluating their environmental friendliness (expressed by persistence, bioaccumulation and migration) and practicability (expressed by insulation). Through the toxicity and estrogen single-activity model validation and contour map analyses, the results showed that the 3D-QSAR model for PAE toxicity and estrogen combined activities was feasible and the weight setting was reasonable. In addition, the mechanism analysis showed that the toxicity and estrogen combined activities of the four DTDP derivatives (2-CH3-DTDP, 2-OCHO-DTDP, 2-CH2COOH-DTDP, 2-CH2OH-DTDP) decreased in turn and were consistent with the single-activity model prediction. Meanwhile, it was speculated that the binding effect of the DTDP derivative molecules and estrogen-related proteins might be related to their hydrophobic interaction.

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Acknowledgements

We thank Wordvice (www.wordvice.cn) for its linguistic assistance during the preparation of this manuscript.

Funding

This study was funded by the Key Projects in the National Science and Technology Pillar Program in the Eleventh Five-Year Plan (grant number 2008BAC43B01).

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Authors and Affiliations

  1. College of Environmental Science and Engineering, North China Electric Power University, Beijing, 02206, China

    Qing Li & Yu Li

  2. MOE Key Laboratory of Resources and Environmental System Optimization, College of Environmental Science and Engineering, North China Electric Power University, Beijing, 102206, China

    Qing Li & Yu Li

  3. Department of Environmental Engineering, North China Institute of Science and Technology, Beijing, 101601, China

    Youli Qiu

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  1. Qing Li
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  2. Youli Qiu
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  3. Yu Li
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Contributions

Conceptualization: Qing Li; Data curation: Qing Li; Formal analysis: Youli Qiu; Methodology: Qing Li; Project administration: Yu Li; Resources: Youli Qiu; Software: Qing Li; Validation: Yu Li; Writing of the original draft: Qing Li; Writing (review and editing): Yu Li

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Correspondence to Yu Li.

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Li, Q., Qiu, Y. & Li, Y. Molecular Design of Environment-Friendly PAE Derivatives Based on 3D-QSAR Assisted with a Comprehensive Evaluation Method Combining Toxicity and Estrogen Activities. Water Air Soil Pollut 231, 194 (2020). https://doi.org/10.1007/s11270-020-04574-2

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