Design, synthesis and fungicidal evaluation of novel pyraclostrobin analogues. Issue 4 (15th February 2018)

• Record Type: Journal Article
• Authors: Wang, Lili; Zhao, Shuangshuang; Kong, Xiaotian; Cao, Lingling; Tian, Sheng; Ye, Yonghao; Qiao, Chunhua
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 4(2018)
• Page Start: 875
• Page End: 883
• Publication Date: 2018-02-15
• Subjects: Antifungal activity -- Pyraclostrobin analogues -- Phytopathogenic fungi -- Cytochrome bc1 complex inhibitor -- Molecular docking; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.01.004
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: Twenty-three novel pyraclostrobin derivatives were designed and prepared as antifungal agents. Compounds5s and5k displayed similar IC50 to positive control pyraclostrobin against certain fungal pathogen. The SAR of these compounds at the side chain position was investigated. Abstract: A series of novel pyraclostrobin derivatives were designed and prepared as antifungal agents. Their antifungal activities were tested in vitro with five important phytopathogenic fungi, namely, Batrylis cinerea, Phytophthora capsici, Fusarium sulphureum, Gloeosporium pestis and Sclerotinia sclerotiorum using the mycelium growth inhibition method. Among these compounds, 5s displayed IC50 value of 0.57 μg/mL against Batrylis cinerea and5k-II displayed IC50 value of 0.43 μg/mL against Sclerotinia sclerotiorum, which were close to that of the positive control pyraclostrobin (0.18 μg/mL and 0.15 μg/mL). Other compounds5f, 5k-II, 5j, 5m and5s also exhibited strong antifungal activity. Further enzymatic assay demonstrated compound5s inhibited porcine bc1 complex with IC50 value of 0.95 μM. The statistical results from an integrated computational pipeline demonstrated the predicted total binding free energy for compound5s is the highest. Consequently, compound5s with the biphenyl-4-methoxyl side chain could serve as a new motif as inhibitors of bc1 complex and deserve to be further investigated.