Design, synthesis and antimicrobial activity of novel quinoline derivatives against phytopathogenic fungi and bacteria inspired from isocryptolepine alkaloids.

BACKGROUND

The natural indoloquinoline alkaloid isocryptolepine has attracted considerable attention owing to its potent bioactivities. Moreover, the development of structural derivatives using natural products as lead compounds constitutes a crucial strategy for discovering new fungicides, which has garnered significant interest from researchers worldwide.

RESULTS

In this study, we designed a series of novel isocryptolepine derivatives via structural simplification of the parent isocryptolepine. These compounds were synthesized and evaluated for antimicrobial efficacy against plant pathogens. Several derivatives showed higher activity than positive control drug. Notably, compound Y-D-29 exhibited outstanding potency with minimum concentration inhibiting 90% bacterial growth values of 3.12 μg mL-1 against Xoo and Xac, surpassing the benchmark agricultural bactericide thiodiazole copper. Mechanistic studies indicated that Y-D-29 inhibited bacterial biofilm formation and significantly reduced exopolysaccharide production in Xoo. Furthermore, propidium iodide and reactive oxygen species (ROS) staining revealed that Y-D-29 disrupted cell membrane integrity and induced lipid peroxidation along with intracellular ROS accumulation.

CONCLUSIONS

Our study indicated that the simplified isocryptolepine analogues, especially Y-D-29, are promising broad-spectrum antibacterial agents for plant disease management. © 2026 Society of Chemical Industry.