Design, Synthesis, and Evaluation of Novel Isothiazole-Purines as a Pyruvate Kinase-Based Fungicidal Lead Compound.

Target identification is one of the most important bases for novel pesticide development; pyruvate kinase (PK) was discovered as a potent fungicide target in our previous studies. To continue the PK-based fungicide development, novel isothiazole-purine derivatives were rationally designed and synthesized. Bioassay results showed that compound displayed excellent activity against with an EC of 1.5 μg/mL, which was superior to those of positive controls diflumetorim with its EC of 19.8 μg/mL and PK-based lead - with its EC of 4.2 μg/mL. Compounds (5.2 μg/mL) and (4.5 μg/mL) displayed better activities against with their ECs falling between 4.0 and 5.5 μg/mL, while showed an EC of 6.4 μg/mL. In addition, exhibited promising activity against and Schw. with 100% efficacy at 10 μg/mL and 90% efficacy at 2 μg/mL against Schw. Compound showed good PK inhibitory activity with an IC of 38.8 μmol/L, and it was well docked into the active site of the target enzyme PK, which was slightly more active than with its IC of 42.4 μmol/L. Our studies discovered that isothiazole-purines were PK-based fungicidal leads deserving of further study.