Details

Autor(en) / Beteiligte

• Wang, Weibo
• Li, Zhixinyi
• Gao, Wei
• Liu, Xiaoyu
• Lv, You
• Hao, Zesheng
• Tang, Liangfu
• Li, Kun
• Zhao, Bin
• Fan, Zhijin

Titel

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

Ist Teil von

• Journal of agricultural and food chemistry, 2021-08, Vol.69 (32), p.9461-9471

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 5ai displayed excellent in vitro activity against Rhizoctonia solani with an EC50 of 1.5 μg/mL, which was superior to those of positive controls diflumetorim with its EC50 of 19.8 μg/mL and PK-based lead YZK-C22 with its EC50 of 4.2 μg/mL. Compounds 3b (5.2 μg/mL) and 3c (4.5 μg/mL) displayed better activities against Gibberella zeae with their EC50s falling between 4.0 and 5.5 μg/mL, while YZK-C22 showed an EC50 of 6.4 μg/mL. In addition, 5ah exhibited promising in vivo activity against Erysiphe graminis and Puccinia sorghi Schw. with 100% efficacy at 10 μg/mL and 90% efficacy at 2 μg/mL against P. sorghi Schw. Compound 5ai showed good PK inhibitory activity with an IC50 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 YZK-C22 with its IC50 of 42.4 μmol/L. Our studies discovered that isothiazole-purines were PK-based fungicidal leads deserving of further study.