Abstract
Chlorinated agrochemicals play a major role in toxicity due especially to the labile C − Cl bond and high lipophilicity of organochlorines. In turn, urea and thiourea herbicides are widely used for weed control. A series of substituted N-benzoyl-N’-pyrimidin-2-yl thioureas has been recently synthesized and tested against Brassica napus L., demonstrating promising herbicidal activities, particularly for chlorinated derivatives. We have therefore modeled these activities using multivariate image analysis applied to quantitative structure–activity relationships (MIA-QSAR) to find out a significant and reliable correlation between measured and predicted inhibition of B. napus L. root growth (%) and, ultimately, to propose effective, non-chlorinated and/or less lipophilic N-(4-methanesulfonyl)benzoyl-N’-(pyrimidin-2-yl)thiourea candidates. The model was found to be predictive, giving an average r2pred in the external validation of 0.833. The predicted data for the proposed herbicides, interpreted in terms of MIA-plots of the chemical moieties responsible for bioactivity and supported by docking studies towards the photosystem II enzyme, suggest that substituents at both R1 and R2 positions modulate the agrochemical (R1 = Cl increases and R2 = OR decreases bioactivity) and environmental friendship (particularly with R2 = OH) performances of this class of compounds.
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Acknowledgements
The authors are thankful to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, funding code 001), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grant number 301371/2017-2), and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) for financial support of this research.
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Natânia E. Rodrigues, Adriana C. de Faria, Ingrid V. Pereira, Elaine F. F. da Cunha and Matheus P. Freitas. The first draft of the manuscript was written by Matheus P. Freitas and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Rodrigues, N.E., de Faria, A.C., Pereira, I.V. et al. QSAR-Guided Proposition of N-(4-methanesulfonyl)Benzoyl-N’-(Pyrimidin-2-yl)Thioureas as Effective and Safer Herbicides. Bull Environ Contam Toxicol 108, 1019–1025 (2022). https://doi.org/10.1007/s00128-022-03467-w
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DOI: https://doi.org/10.1007/s00128-022-03467-w