Structural optimization of SDH-targeting chalcone derivatives: piperazine-driven binding stability against...

Area of Science:

• Agrochemicals
• Medicinal Chemistry
• Plant Pathology

Background:

• Natural pesticides are a key research area.
• Identifying novel chemical structures with biological activity is crucial for developing new agrochemicals.

Purpose of the Study:

• To synthesize and evaluate chalcone derivatives with 1,2,3,4-tetrahydroquinoline scaffolds for antibacterial activity.
• To identify potent compounds for agricultural antimicrobial applications.

Main Methods:

• Systematic evaluation of 20 chalcone derivatives against six plant pathogenic bacteria.
• In vitro and in vivo efficacy testing.
• Scanning electron microscopy for membrane integrity analysis.
• Molecular docking and dynamics simulations targeting succinate dehydrogenase (SDH).

Main Results:

• Compound H6 demonstrated superior in vitro antibacterial activity against Xanthomonas citri pv. mangiferaeindicae (Xcm) (EC50 = 3.25 μg/mL) compared to commercial agents.
• H6 showed significant in vivo curative activity (65.24%) and disrupted bacterial membrane integrity.
• Molecular simulations revealed H6's strong binding affinity to SDH, similar to the commercial inhibitor bixafen.

Conclusions:

• The 1,2,3,4-tetrahydroquinoline scaffold enhances SDH binding.
• H6's piperazine substructure improves complex stability and target engagement.
• H6 is a promising lead compound for developing novel SDH inhibitors for agricultural antimicrobial applications.