Synthesis and Biological Activity of Novel Pyrazolo[3,4-d]pyrimidin-4-one Derivatives as Potent Antifungal Agent.

BACKGROUND To promote the discovery and development of new fungicide with novel scaffolds or modes of action, a series of novel 5-(2-chloroethyl)-1-phenyl-6-(pyridin-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized, and evaluated for their antifungal activities. RESULTS The bioassay data showed that compound 8IIId (EC50 = 1.93 mg/L) is superior to boscalid (EC50 = 6.71 mg/L) against Valsa mali. We introduced chiral groups on the structure of 8IIId, and two chiral configurations were respectively synthesized, which are 8Vc and 8Vd. Surprisingly, 8Vc showed significant antifungal activities against Valsa mali and Physalospora piricola with EC50 values of 0.22 and 0.55 mg/L. Physiological and biochemical studies showed that the primary action mechanism of compound 8Vc on Valsa mali may involve changing mycelial morphology and increasing cell membrane permeability. CONCLUSION These results demonstrated that 8Vc could be further modified as fungicide and provided a valuable reference for antifungal agents with pyrazolo[3,4-d]pyrimidin-4-one skeleton.