Novel Cyclopropyl-Uracil Derivatives as Potent Herbicides: Design, Synthesis, Activity, and Structure-Activity...

Area of Science:

• Agricultural Chemistry
• Organic Synthesis
• Plant Science

Background:

• Herbicides are essential for effective weed management in agriculture.
• Developing novel herbicides with improved efficacy and selectivity is a continuous goal.

Purpose of the Study:

• To design and synthesize novel cycloalkyl-substituted pyrimidinedione derivatives as potential herbicidal leads.
• To evaluate the herbicidal activity of these compounds against broadleaf and grass weeds.

Main Methods:

• Molecular hybridization was employed to design 37 cycloalkyl-substituted pyrimidinedione derivatives.
• Greenhouse assays were conducted to assess postemergence herbicidal activity.
• In vitro enzyme inhibition assays determined protoporphyrinogen oxidase (PPO) inhibitory activity.
• Molecular docking and density functional theory (DFT) calculations were used for mechanistic insights.

Main Results:

• All synthesized compounds exhibited significant postemergence activity against broadleaf weeds.
• Several derivatives showed promising activity against grass weeds.
• Compound 9i demonstrated superior efficacy compared to the standard herbicide tiafenacil, achieving 100% control of Zinnia elegans and Abutilon theophrasti at 2.34 g a.i./ha.
• Compound 9i showed 90% control of Echinochloa crus-galli at 9.38 g a.i./ha.
• While compound 9i's PPO inhibition (IC50 = 9.55 nM) was slightly weaker than tiafenacil (6.85 nM), its in vivo efficacy was superior.
• Molecular docking suggested a conserved binding mode with PPO, potentially involving an additional hydrogen bond.
• DFT calculations indicated that compound 9i's high clogP (4.34) enhances plant penetration and transmembrane transport.

Conclusions:

• Compound 9i represents a highly effective herbicidal lead with excellent in vivo performance.
• The enhanced herbicidal activity of compound 9i is attributed to its favorable physicochemical properties facilitating plant uptake, rather than solely stronger PPO inhibition.
• These findings highlight the potential of cycloalkyl-substituted pyrimidinediones for developing next-generation herbicides.