Leveraging Natural Product-inspired Antifungals to Investigate the Mechanism of Action of Peniciaculin A.

IF 3.6 4区 医学 Q2 CHEMISTRY, MEDICINAL ChemMedChem Pub Date : 2024-09-05 DOI:10.1002/cmdc.202400500
Ingrid Wilt, Adrian Demeritte, Alexander Kim, Weiwei Wang, William M Wuest
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Abstract

Ubiquinone mimics known as quinone outside inhibitors (QoIs) are one of the most prominent fungicides used to protect crops in the agricultural industry. Due to chemotype similarities with known QoIs, peniciaculin A, a triaryl natural product, was proposed to exhibit similar broad spectrum antifungal activity against phytopathogens. Instability of the tertiary alcohol and phenol motif, however, prompted exploration of the antifungal properties of simplified analogues to probe possible overlap in mechanism of action between the natural product and QoIs. Peniciaculin A inspired analogues mimicking known QoI scaffolds displayed broad spectrum antifungal activity while those containing scaffolds dissimilar to QoIs possessed negligible bioactivity. These activity profiles suggest peniciaculin A is likely acting as a QoI.

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利用天然产品启发的抗真菌药物研究青霉素 A 的作用机制。
被称为醌外抑制剂(QoIs)的泛醌模拟物是农业领域用于保护农作物的最重要的杀真菌剂之一。由于与已知 QoIs 的化学型相似,有人提出三芳基天然产物 peniciaculin A 对植物病原体具有类似的广谱抗真菌活性。然而,叔醇和苯酚基团的不稳定性促使人们探索简化类似物的抗真菌特性,以探究天然产物和 QoIs 之间可能存在的作用机制重叠。模仿已知 QoI 骨架的青霉素 A 灵感类似物显示出广谱抗真菌活性,而那些含有与 QoI 不同骨架的类似物的生物活性则微乎其微。这些活性特征表明,青霉素 A 很可能是一种 QoI。
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来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
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