Scaffold Hopping from Dehydrozingerone: Design, Synthesis, and Antifungal Activity of Phenoxyltrifluoromethylpyridines

Nan, Xiaohui; Wang, Kaifeng; Sun, Xinru; Hu, Zhan; Sun, Ranfeng

doi:10.3390/ijms26115345

Open AccessArticle

Scaffold Hopping from Dehydrozingerone: Design, Synthesis, and Antifungal Activity of Phenoxyltrifluoromethylpyridines

by

Xiaohui Nan

^†,

Kaifeng Wang

^†

,

Xinru Sun

,

Zhan Hu

^*

and

Ranfeng Sun

^*

Key Laboratory of Green Prevention and Control of Tropical Plant Diseases and Pests, Ministry of Education, School of Tropical Agriculture and Forestry, Hainan University, Danzhou 571737, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2025, 26(11), 5345; https://doi.org/10.3390/ijms26115345

Submission received: 25 April 2025 / Revised: 23 May 2025 / Accepted: 30 May 2025 / Published: 2 June 2025

(This article belongs to the Special Issue Green Chemical Pesticide Design, Synthesis and Evaluation)

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Abstract

In response to the urgent need for innovative fungicides to ensure food security and safety, a series of twenty-three novel trifluoromethylpyridine compounds were designed and synthesized using a scaffold hopping strategy derived from dehydrozingerone. This approach involved converting the α, β-unsaturated ketone moiety into a pyridine ring. Bioassay results indicated that the majority of these compounds exhibited promising in vitro antifungal activity, particularly against Rhizoctonia solani and Colletotrichum musae. Notably, compound 17 showed the highest efficacy and broad-spectrum activity, with median effective concentrations (EC₅₀) ranging from 2.88 to 9.09 μg/mL. Phenoxytrifluoromethylpyridine derivatives, including compound 17, exhibited superior antifungal activity compared to benzyloxytrifluoromethylpyridine derivatives. In vivo tests revealed that both compounds 17 and 23 exhibited moderate control effects against C. musae. The degradation half-lives of compounds 17 and 23 in bananas were determined to be 176.9 h and 94.8 h, respectively, indicating the stability of their structures in the environment. Molecular docking studies indicated that compound 23 interacts with succinate dehydrogenase, offering valuable insights for the structural optimization of compound 23.

Keywords: scaffold hopping; trifluoromethyl dehydrozingerone; phenoxytrifluoromethylpyridine; antifungal activity; molecular docking

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MDPI and ACS Style

Nan, X.; Wang, K.; Sun, X.; Hu, Z.; Sun, R. Scaffold Hopping from Dehydrozingerone: Design, Synthesis, and Antifungal Activity of Phenoxyltrifluoromethylpyridines. Int. J. Mol. Sci. 2025, 26, 5345. https://doi.org/10.3390/ijms26115345

AMA Style

Nan X, Wang K, Sun X, Hu Z, Sun R. Scaffold Hopping from Dehydrozingerone: Design, Synthesis, and Antifungal Activity of Phenoxyltrifluoromethylpyridines. International Journal of Molecular Sciences. 2025; 26(11):5345. https://doi.org/10.3390/ijms26115345

Chicago/Turabian Style

Nan, Xiaohui, Kaifeng Wang, Xinru Sun, Zhan Hu, and Ranfeng Sun. 2025. "Scaffold Hopping from Dehydrozingerone: Design, Synthesis, and Antifungal Activity of Phenoxyltrifluoromethylpyridines" International Journal of Molecular Sciences 26, no. 11: 5345. https://doi.org/10.3390/ijms26115345

APA Style

Nan, X., Wang, K., Sun, X., Hu, Z., & Sun, R. (2025). Scaffold Hopping from Dehydrozingerone: Design, Synthesis, and Antifungal Activity of Phenoxyltrifluoromethylpyridines. International Journal of Molecular Sciences, 26(11), 5345. https://doi.org/10.3390/ijms26115345

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Scaffold Hopping from Dehydrozingerone: Design, Synthesis, and Antifungal Activity of Phenoxyltrifluoromethylpyridines

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