Design and Synthesis of Potential Quinoline-Based SDH Inhibitors Inspired by Quinine Alkaloids with Activity against Phytopathogenic Fungi and Bacteria

Abstract

In pursuit of environmentally friendly agrochemicals, we employed the natural quinine alkaloid scaffold as a lead for the design and synthesis of three series of structurally diverse quinine derivatives and systematically evaluated their in vitro antibacterial and antifungal activities. Among them, compounds Ka9 and Ka10 exhibited good antibacterial activity, with MIC values of 6.25 μg/mL against both Xoo and Xac, while compound Kc1 exhibited excellent activity against Magnaporthe oryzae (EC50 = 2.56 μg/mL) and effectively inhibited succinate dehydrogenase (SDH). Furthermore, molecular docking and dynamics simulations revealed that Kc1 shares a similar binding mode with boscalid in the SDH active site. These findings highlight Kc1 as a promising quinoline-based lead compound for further development and provide a scientific rationale for repurposing natural product scaffolds in sustainable plant protection.