QSAR-Guided Proposition of N-(4-methanesulfonyl)Benzoyl-N’-(Pyrimidin-2-yl)Thioureas as Effective and Safer Herbicides

• Published in: Bulletin of environmental contamination and toxicology 2022-06, Vol.108 (6), p.1019-1025
• Main Authors: Rodrigues, Natânia E., de Faria, Adriana C., Pereira, Ingrid V., da Cunha, Elaine F. F., Freitas, Matheus P.
• Format: Article
• Language: English
• Subjects: Agrochemicals; Aquatic Pollution; Biocompatibility; Biological activity; Brassica; Chlorination; Earth and Environmental Science; Ecotoxicology; Environment; Environmental Chemistry; Environmental Health; Herbicides; Image analysis; Image processing; Lipophilic; Lipophilicity; Organochlorine compounds; Photosystem II; Plant growth; Pollution; Soil Science & Conservation; Structure-activity relationships; Thiourea; Thioureas; Toxicity; Urea; Waste Water Technology; Water Management; Water Pollution Control; Weed control
• ISSN: 0007-4861; 1432-0800
• DOI: 10.1007/s00128-022-03467-w

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 r 2 pred 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 R 1 and R 2 positions modulate the agrochemical (R 1  = Cl increases and R 2  = OR decreases bioactivity) and environmental friendship (particularly with R 2  = OH) performances of this class of compounds.