Second-Generation Enamine-Type Schiff Bases as 2-Amino Acid-Derived Antifungals against <i>Fusarium oxysporum</i>: Microwave-Assisted Synthesis, In Vitro Activity, 3D-QSAR, and In Vivo Effect
In this manuscript, the synthesis of enamine-type Schiff bases <b>1–48</b> derived from the amino acids <i>L</i>-Ala, <i>L</i>-Tyr, and <i>L</i>-Phe was carried out. Their in vitro activity and in vivo protective effect against <i>Fusarium oxyspo...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/1/113 |
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| author | Paola Borrego-Muñoz Diego Cardenas Felipe Ospina Ericsson Coy-Barrera Diego Quiroga |
| author_facet | Paola Borrego-Muñoz Diego Cardenas Felipe Ospina Ericsson Coy-Barrera Diego Quiroga |
| author_sort | Paola Borrego-Muñoz |
| collection | DOAJ |
| description | In this manuscript, the synthesis of enamine-type Schiff bases <b>1–48</b> derived from the amino acids <i>L</i>-Ala, <i>L</i>-Tyr, and <i>L</i>-Phe was carried out. Their in vitro activity and in vivo protective effect against <i>Fusarium oxysporum</i> were also evaluated through mycelial growth inhibition and disease severity reduction under greenhouse conditions. The in vitro activity of test compounds <b>1–48</b> showed half-maximal inhibitory concentrations (IC<sub>50</sub>) at different levels below the 40 mM range. Deep analysis of the IC<sub>50</sub> variations indicated that the size of the substituent on the acetylacetone derivatives and the electronic character on the cyclohexane-3-one fragment influenced the antifungal effect. 3D-QSAR models based on atoms (atom-based approach) were built to establish the structure–activity relationship of the test Schiff bases, showing a good correlation and predictive consistency (R<sup>2</sup> > 0.70 and Q<sup>2</sup> > 0.60). The respective contour analysis also provided information about the structural requirements for potentiating their antifungal activity. In particular, the amino acid-related fragment and the alkyl ester residue can favor hydrophobic interactions. In contrast, the nitrogen atoms and enamine substituent are favorable regions as <i>H</i>-donating and electron-withdrawing moieties. The most active compounds (<b>40</b> and <b>41</b>) protected cape gooseberry plants against <i>F. oxysporum</i> infection (disease severity index < 2), involving adequate physiological parameters (stomatal conductance > 150 mmol/m<sup>2</sup>s) after 45 days of inoculation. These promising results will allow the design of novel Schiff base-inspired antifungals using 2-amino acids as precursors. |
| first_indexed | 2024-03-09T12:04:02Z |
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| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T12:04:02Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
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| series | Journal of Fungi |
| spelling | doaj.art-c1fb08b7837d44e581c1ff9945fd9fc12023-11-30T23:00:30ZengMDPI AGJournal of Fungi2309-608X2023-01-019111310.3390/jof9010113Second-Generation Enamine-Type Schiff Bases as 2-Amino Acid-Derived Antifungals against <i>Fusarium oxysporum</i>: Microwave-Assisted Synthesis, In Vitro Activity, 3D-QSAR, and In Vivo EffectPaola Borrego-Muñoz0Diego Cardenas1Felipe Ospina2Ericsson Coy-Barrera3Diego Quiroga4Bioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Campus Nueva Granada, Cajicá 250247, ColombiaBioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Campus Nueva Granada, Cajicá 250247, ColombiaBioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Campus Nueva Granada, Cajicá 250247, ColombiaBioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Campus Nueva Granada, Cajicá 250247, ColombiaBioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Campus Nueva Granada, Cajicá 250247, ColombiaIn this manuscript, the synthesis of enamine-type Schiff bases <b>1–48</b> derived from the amino acids <i>L</i>-Ala, <i>L</i>-Tyr, and <i>L</i>-Phe was carried out. Their in vitro activity and in vivo protective effect against <i>Fusarium oxysporum</i> were also evaluated through mycelial growth inhibition and disease severity reduction under greenhouse conditions. The in vitro activity of test compounds <b>1–48</b> showed half-maximal inhibitory concentrations (IC<sub>50</sub>) at different levels below the 40 mM range. Deep analysis of the IC<sub>50</sub> variations indicated that the size of the substituent on the acetylacetone derivatives and the electronic character on the cyclohexane-3-one fragment influenced the antifungal effect. 3D-QSAR models based on atoms (atom-based approach) were built to establish the structure–activity relationship of the test Schiff bases, showing a good correlation and predictive consistency (R<sup>2</sup> > 0.70 and Q<sup>2</sup> > 0.60). The respective contour analysis also provided information about the structural requirements for potentiating their antifungal activity. In particular, the amino acid-related fragment and the alkyl ester residue can favor hydrophobic interactions. In contrast, the nitrogen atoms and enamine substituent are favorable regions as <i>H</i>-donating and electron-withdrawing moieties. The most active compounds (<b>40</b> and <b>41</b>) protected cape gooseberry plants against <i>F. oxysporum</i> infection (disease severity index < 2), involving adequate physiological parameters (stomatal conductance > 150 mmol/m<sup>2</sup>s) after 45 days of inoculation. These promising results will allow the design of novel Schiff base-inspired antifungals using 2-amino acids as precursors.https://www.mdpi.com/2309-608X/9/1/113Schiff baseenamine2-amino acidsantifungal activity<i>Fusarium oxysporum</i>QSAR-3D |
| spellingShingle | Paola Borrego-Muñoz Diego Cardenas Felipe Ospina Ericsson Coy-Barrera Diego Quiroga Second-Generation Enamine-Type Schiff Bases as 2-Amino Acid-Derived Antifungals against <i>Fusarium oxysporum</i>: Microwave-Assisted Synthesis, In Vitro Activity, 3D-QSAR, and In Vivo Effect Journal of Fungi Schiff base enamine 2-amino acids antifungal activity <i>Fusarium oxysporum</i> QSAR-3D |
| title | Second-Generation Enamine-Type Schiff Bases as 2-Amino Acid-Derived Antifungals against <i>Fusarium oxysporum</i>: Microwave-Assisted Synthesis, In Vitro Activity, 3D-QSAR, and In Vivo Effect |
| title_full | Second-Generation Enamine-Type Schiff Bases as 2-Amino Acid-Derived Antifungals against <i>Fusarium oxysporum</i>: Microwave-Assisted Synthesis, In Vitro Activity, 3D-QSAR, and In Vivo Effect |
| title_fullStr | Second-Generation Enamine-Type Schiff Bases as 2-Amino Acid-Derived Antifungals against <i>Fusarium oxysporum</i>: Microwave-Assisted Synthesis, In Vitro Activity, 3D-QSAR, and In Vivo Effect |
| title_full_unstemmed | Second-Generation Enamine-Type Schiff Bases as 2-Amino Acid-Derived Antifungals against <i>Fusarium oxysporum</i>: Microwave-Assisted Synthesis, In Vitro Activity, 3D-QSAR, and In Vivo Effect |
| title_short | Second-Generation Enamine-Type Schiff Bases as 2-Amino Acid-Derived Antifungals against <i>Fusarium oxysporum</i>: Microwave-Assisted Synthesis, In Vitro Activity, 3D-QSAR, and In Vivo Effect |
| title_sort | second generation enamine type schiff bases as 2 amino acid derived antifungals against i fusarium oxysporum i microwave assisted synthesis in vitro activity 3d qsar and in vivo effect |
| topic | Schiff base enamine 2-amino acids antifungal activity <i>Fusarium oxysporum</i> QSAR-3D |
| url | https://www.mdpi.com/2309-608X/9/1/113 |
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