Design, synthesis, X-ray crystal structure, and antifungal evaluation of new acetohydrazide derivatives containing a 4-thioquinazoline moiety.

BACKGROUND

To find efficient agricultural fungicides, 29 new 4-thioquinazoline-containing acetohydrazide derivatives were prepared and tested for their fungicidal properties.

RESULTS

All of the target compounds were characterized by H and C nuclear magnetic resonance and high-resolution mass spectrometry techniques, and the molecular structure of compound A2 was verified by single-crystal X-ray diffraction measurement. The experimental results revealed that many compounds from this series had impressive inhibition efficacies in vitro against the tested fungi. For example, compound A25 was identified as the best fungicidal agent against Rhizoctonia solani with an EC (half-maximal effective concentration) value of 0.66 μg mL, superior to those of the commercial fungicides chlorothalonil, carbendazim and boscalid. Additionally, this compound displayed favorable protection and curative activities in vivo against rice sheath blight caused by R. solani. Antifungal mechanistic studies on compound A25 indicated that this compound exerted its strong anti-R. solani effects probably through an effective inhibition of fungal succinate dehydrogenase activity [half-maximal inhibitory concentration (IC) = 4.88 μm] and the impairment of cell membrane integrity, based on the results from enzymatic bioassays, molecular docking studies, and scanning and transmission electron microscopy observations.

CONCLUSION

Acetohydrazide derivatives containing the 4-thioquinazoline moiety had the potential to be employed as lead compounds for developing more efficient agricultural fungicides in the near future. © 2024 Society of Chemical Industry.