Design, synthesis and antimicrobial activity evaluation of novel Marinoquinoline derivatives against phytopathogenic bacteria

Pest Manag Sci. 2024 Dec 27. doi: 10.1002/ps.8609. Online ahead of print.

Abstract

Background: Plant diseases caused by plant pathogens pose a great threat to biodiversity and food security, and the problem of drug resistance caused by traditional antibiotics and fungicides is becoming more and more serious. It is urgent to develop new antibacterial molecules with low toxicity and high efficiency. Marinoquinoline A is an alkaloid isolated from marine actinomycetes and has a variety of pharmacological activities. In this study, a series of compounds were designed and synthesized by fragment fusion strategy inspired by Marinoquinoline, and their antibacterial activities were evaluated, and the structure-activity relationship was discussed.

Results: Among these derivatives, ZM-9 showed the most significant antibacterial activity against Xanthomonas oryzae (Xoo) with MIC of 1.56 μg mL-1, while ZN-8 showed the best antibacterial activity against Xanthomonas axonopodis pv. Citri (Xac) with MIC of 0.78 μg mL-1, both of which were better than Thiodiazole copper. The results of in vivo antibacterial activity test showed that 200 μg mL-1 ZM-9 and ZN-8 had significant control effects on rice and citrus. The biochemical experiments showed that ZM-9 and ZN-8 could inhibit the secretion of extracellular polysaccharides, destroy the biofilm integrity of the pathogens, increase permeability, and cause oxidative stress damage.

Conclusion: In summary, most of the chemical entities inspired by Marinoquinoline have shown good antibacterial activity. In particular, compounds ZM-9 and ZN-8 can be used as lead compounds for further structural optimization to develop new antibacterial agents. © 2024 Society of Chemical Industry.

Keywords: 1,3‐diamino‐7H‐pyrrolo[3,2‐f]quinazoline; Marinoquinoline; antimicrobial activity; mechanism of action; phytopathogenic bacteria.