Synthesis, antibacterial evaluation and preliminary mechanism study of novel isoquinoline-3-carboxylic acid derivatives containing an acylhydrazone disulfone moiety

BACKGROUND

Limitations in the use and availability of copper-based fungicides and antibiotics has led to a scarcity of bactericidal agents. It is urgent to develop green bactericides with new modes-of-action and effective chemotypes.

RESULTS

A bioactive substructure splicing approach was applied to optimize the structure of the natural product isoquinolin-3-carboxylic acid (IQ3CA). The structure–activity relationship analysis showed that the increase of sulfur atomic oxidation state and small groups on the sulfone will be beneficial for antibacterial activities. The difulone compound SF2 showed the most potent activity against Xanthomonas oryzae pv. oryzae (Xoo), Ralstonia solanacearum (Rs) and Acidovorax citrulli (Ac), with median lethal effective concentration values of 2.52, 2.62 and 1.12 μg mL⁻¹, respectively, which were superior to those of IQ3CA and kasugamycin. The protective and curative effects of compound SF2 against Ac were 69.31% and 55.64%, respectively, which were better than those of thiodiazole copper (58.37% and 43.08%). Furthermore, preliminary mechanistic investigations indicated that compound SF2 could increase membrane permeability, reduce exopolysaccharide content, and inhibit both bacterial motility and biofilm formation.

CONCLUSIONS

A series of novel isoquinoline-3-acylhydrazone derivatives incorporating thioether/disulfone moieties were synthesized, and bioassay results showed compound SF2 demonstrated remarkable antibacterial activity by disrupting bacterial membranes. © 2025 Society of Chemical Industry.