Triphenylphosphonium-Driven Targeting of Pyrimorph Fragment Derivatives Greatly Improved Its Action on Phytopathogen...

Area of Science:

• Agricultural Science
• Mycology
• Biochemistry

Background:

• Pyrimorph, a carboxylic acid amide (CAA) fungicide, effectively controls oomycete plant pathogens by inhibiting cell wall biosynthesis.
• While pyrimorph has weak mitochondrial complex III inhibition, this study explores enhancing its mitochondrial action for novel fungicide development.

Purpose of the Study:

• To design and synthesize novel mitochondrial-targeting analogues of pyrimorph.
• To investigate the structure-activity relationship for improved fungicidal and mitochondrial inhibitory effects.
• To develop new fungicides with enhanced mitochondrial action and potentially novel mechanisms of action.

Main Methods:

• Disassembly of pyrimorph and conjugation with a triphenylphosphonium mitochondrial delivery system.
• Synthesis of three series of mitochondrial-targeting pyrimorph analogues.
• Evaluation of fungicidal activity, respiratory inhibition, and adenosine 5'-triphosphate synthesis inhibition.

Main Results:

• The pyridine-containing 1,1-diaryl moiety was identified as the core for inhibiting mitochondrial function.
• Compound 3b, featuring a short linker, exhibited the highest broad-spectrum fungicidal and respiratory inhibition activity.
• Compound 3b demonstrated significant mitochondrial disruption, including swelling and impaired function, leading to reduced cell wall impact.

Conclusions:

• Mitochondrial targeting significantly enhances the fungicidal efficacy of pyrimorph analogues.
• Compound 3b represents a promising fungicide candidate with potent and broad-spectrum activity.
• This approach provides a valuable strategy for developing novel mitochondrial bioactive molecules and pesticides with improved efficacy.