Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates.
Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates.
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DOI：
10.1021/acs.jafc.3c02096
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发表时间：
2023-07
影响因子：
6.1
通讯作者：
Chen-Hwa Yang;Shengxin Sun;Wei Li;Y. Mao;Qiao Wang;Y. Duan;R. Csuk;Shengkun Li
中科院分区：
文献类型：
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作者：
Chen-Hwa Yang;Shengxin Sun;Wei Li;Y. Mao;Qiao Wang;Y. Duan;R. Csuk;Shengkun Li
新的和容易获得的线索的发现为农业化学品创新提供了令人信服的解决方案。对先前的“Chem-Bio Model”异喹啉-3-恶唑啉MIQOX进行生物测定引导的支架减法，以鉴定容易获得的异喹啉-3-酰肼作为新型抗真菌支架。通过表型抗真菌生物测定、分子对接和交叉耐药性评价，证明了该模型的特殊性和实用潜力。获得了一组抗真菌先导化合物（LW 2、LW 3和LW 11），显示出比阳性对照好得多的抗真菌性能。具体地，化合物LW 3表现出宽的抗真菌谱，其对B的EC 50值低至0.54、0.09、1.52和2.65 mg/L。cinerea、灰毛苔草R. solani，S. sclerotiorum和F. graminearum，分别。对B引起的植物病害的防治效果优于啶酰菌胺。灰色区域。LW 3对常用的琥珀酸脱氢酶抑制剂（SDHI）无交互抗性，能有效抑制抗性B。灰霉病菌株化合物LW 3的分子对接与阳性对照啶酰菌胺和氟吡菌酰胺的分子对接完全不同。这一进展突出了异喹啉酰肼作为杀菌剂创新新模式的实用性。
The discovery of novel and easily available leads provides a convincing solution to agrochemical innovation. A bioassay-guided scaffold subtraction of the previous "Chem-Bio Model" isoquinoline-3-oxazoline MIQOX was conducted for identifying the easily available isoquinoline-3-hydrazide as a novel antifungal scaffold. The special and practical potential of this model was demonstrated by a phenotypic antifungal bioassay, molecular docking, and cross-resistance evaluation. A panel of antifungal leads (LW2, LW3, and LW11) was acquired, showing much better antifungal performance than the positive controls. Specifically, compound LW3 exhibited a broad antifungal spectrum holding EC50 values as low as 0.54, 0.09, 1.52, and 2.65 mg/L against B. cinerea, R. solani, S. sclerotiorum , and F. graminearum, respectively. It demonstrated a curative efficacy better than that of boscalid in controlling the plant disease caused by B. cinerea. The candidate LW3 did not show cross-resistance to the extensively used succinate dehydrogenase inhibitor (SDHI) fungicides and can efficiently inhibit resistant B. cinerea strains. The molecular docking of compound LW3 is quite different from that of the positive controls boscalid and fluopyram. This progress highlights the practicality of isoquinoline hydrazide as a novel model in fungicide innovation.