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

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(pred)(2) 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.

Automated summary

Recent research has shown promising herbicidal activities, particularly for chlorinated derivatives, in a series of substituted N-benzoyl-N'-pyrimidin-2-yl thioureas tested against Brassica napus L. The study utilized multivariate image analysis to predict inhibition of root growth and propose effective non-chlorinated candidates. The model was found to be predictive, with an average r(pred)(2) in external validation of 0.833.