Synthesis of Novel Stilbene-Coumarin Derivatives and Antifungal Screening of <i>Monotes kerstingii</i>-Specialized Metabolites Against <i>Fusarium oxysporum</i>

• Main Authors: Ghislain Wabo Fotso (Author), Bathelemy Ngameni (Author), Thomas E. Storr (Author), Bonaventure Tchaleu Ngadjui (Author), Sibongile Mafu (Author), G. Richard Stephenson (Author)
• Format: Book
• Published: MDPI AG, 2020-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics9090537; 2079-6382
• Keywords: <i>Monotes kerstingii</i>; antifungal activity; <i>Fusarium oxysporum</i>; semisynthesis; stilbene-coumarins; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 9, Iss 9, p 537 (2020)

<i>Fusarium</i> is one of the most toxigenic phytopathogens causing diseases and reduced agricultural productivity worldwide. Current chemical fungicides exhibit toxicity against non-target organisms, triggering negative environmental impact, and are a danger to consumers. In order to explore the chemical diversity of plants for potential antifungal applications, crude extract and fractions from <i>Monotes kerstingii</i> were screened for their activity against two multi-resistant <i>Fusarium oxysporum</i> strains: <i>Fo32931</i> and <i>Fo4287</i>. Antifungal activity was evaluated by the determination of minimum inhibitory concentration (MIC) by broth dilution of fermentative yeasts using kinetic OD_{600 nm} reading by a spectrophotometer. The <i>n</i>-butanol fraction showed the best activity against <i>Fo4287</i>. We screened eleven previously reported natural compounds isolated from different fractions, and a stilbene-coumarin 5-[(1<i>E</i>)-2-(4-hydroxyphenyl)ethenyl]-4,7-dimethoxy-3-methyl-2<i>H</i>-1-benzopyran-2-one (<b>1</b>) was the most active compound against both strains. Compound <b>1</b> was employed as a nucleophile with a selection of electrophilic derivatizing agents to synthesize five novel stilbene-coumarin analogues. These semisynthetic derivatives showed moderate activity against <i>Fo32931</i> with only prenylated derivative exhibiting activity comparable to the natural stilbene-coumarin (<b>1</b>), demonstrating the key role of the phenolic group.