Synthesis and Antifungal Activity of Fmoc-Protected 1,2,4-Triazolyl-α-Amino Acids and Their Dipeptides Against <i>Aspergillus</i> Species
In recent years, fungal infections have emerged as a significant health concern across veterinary species, especially in livestock such as cattle, where fungal diseases can result in considerable economic losses, as well as in humans. In particular, <i>Aspergillus</i> species, notably &l...
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2025-01-01
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| author | Tatevik Sargsyan Lala Stepanyan Henrik Panosyan Heghine Hakobyan Monika Israyelyan Avetis Tsaturyan Nelli Hovhannisyan Caterina Vicidomini Anna Mkrtchyan Ashot Saghyan Giovanni N. Roviello |
| author_facet | Tatevik Sargsyan Lala Stepanyan Henrik Panosyan Heghine Hakobyan Monika Israyelyan Avetis Tsaturyan Nelli Hovhannisyan Caterina Vicidomini Anna Mkrtchyan Ashot Saghyan Giovanni N. Roviello |
| author_sort | Tatevik Sargsyan |
| collection | DOAJ |
| description | In recent years, fungal infections have emerged as a significant health concern across veterinary species, especially in livestock such as cattle, where fungal diseases can result in considerable economic losses, as well as in humans. In particular, <i>Aspergillus</i> species, notably <i>Aspergillus flavus</i> and <i>Aspergillus versicolor</i>, are opportunistic pathogens that pose a threat to both animals and humans. This study focuses on the synthesis and antifungal evaluation of novel 9-fluorenylmethoxycarbonyl (Fmoc)-protected 1,2,4-triazolyl-α-amino acids and their dipeptides, designed to combat fungal pathogens. More in detail, we evaluated their antifungal activity against various species, including <i>Aspergillus versicolor</i> (ATCC 12134) and <i>Aspergillus flavus</i> (ATCC 10567). The results indicated that dipeptide <b>7a</b> exhibited promising antifungal activity against <i>Aspergillus versicolor</i> with an IC<sub>50</sub> value of 169.94 µM, demonstrating greater potency than fluconazole, a standard treatment for fungal infections, which showed an IC<sub>50</sub> of 254.01 µM. Notably, dipeptide <b>7a</b> showed slightly enhanced antifungal efficacy compared to fluconazole also in <i>Aspergillus flavus</i> (IC<sub>50</sub> 176.69 µM vs. 184.64 µM), suggesting that this dipeptide might be more potent even against this strain. Remarkably, <b>3a</b> and <b>7a</b> are also more potent than fluconazole against <i>A. candidus</i> 10711. On the other hand, the protected amino acid <b>3a</b> demonstrated consistent inhibition across all tested <i>Aspergillus</i> strains, but with an IC<sub>50</sub> value of 267.86 µM for <i>Aspergillus flavus</i>, it was less potent than fluconazole (IC<sub>50</sub> 184.64 µM), still showing some potential as a good antifungal molecule. Overall, our findings indicate that the synthesized 1,2,4-triazolyl derivatives <b>3a</b> and <b>7a</b> hold significant promise as potential antifungal agents in treating <i>Aspergillus</i>-induced diseases in cattle, as well as for broader applications in human health. Our mechanistic studies based on molecular docking revealed that compounds <b>3a</b> and <b>7a</b> bind to the same region of the sterol 14-α demethylase as fluconazole. Given the rising concerns about antifungal resistance, these amino acid derivatives, with their unique bioactive structures, could serve as a novel class of therapeutic agents. Further research into their in vivo efficacy and safety profiles is warranted to fully realize their potential as antifungal drugs in clinical and agricultural settings. |
| format | Article |
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| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
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| series | Biomolecules |
| spelling | doaj-art-c9db507e6770429bb0920ba8622ae09f2025-01-24T13:25:02ZengMDPI AGBiomolecules2218-273X2025-01-011516110.3390/biom15010061Synthesis and Antifungal Activity of Fmoc-Protected 1,2,4-Triazolyl-α-Amino Acids and Their Dipeptides Against <i>Aspergillus</i> SpeciesTatevik Sargsyan0Lala Stepanyan1Henrik Panosyan2Heghine Hakobyan3Monika Israyelyan4Avetis Tsaturyan5Nelli Hovhannisyan6Caterina Vicidomini7Anna Mkrtchyan8Ashot Saghyan9Giovanni N. Roviello10Scientific and Production Center “Armbiotechnology” NAS RA, 14 Gyurjyan Str., Yerevan 0056, ArmeniaScientific and Production Center “Armbiotechnology” NAS RA, 14 Gyurjyan Str., Yerevan 0056, ArmeniaScientific Technological Center of Organic and Pharmaceutical Chemistry, 26, Azatutian Ave., Yerevan 0014, ArmeniaScientific and Production Center “Armbiotechnology” NAS RA, 14 Gyurjyan Str., Yerevan 0056, ArmeniaScientific and Production Center “Armbiotechnology” NAS RA, 14 Gyurjyan Str., Yerevan 0056, ArmeniaScientific and Production Center “Armbiotechnology” NAS RA, 14 Gyurjyan Str., Yerevan 0056, ArmeniaScientific and Production Center “Armbiotechnology” NAS RA, 14 Gyurjyan Str., Yerevan 0056, ArmeniaInstitute of Biostructures and Bioimaging, Italian National Council for Research (IBB-CNR), Area di Ricerca Site and Headquarters, Via Pietro Castellino 111, 80131 Naples, ItalyScientific and Production Center “Armbiotechnology” NAS RA, 14 Gyurjyan Str., Yerevan 0056, ArmeniaScientific and Production Center “Armbiotechnology” NAS RA, 14 Gyurjyan Str., Yerevan 0056, ArmeniaInstitute of Biostructures and Bioimaging, Italian National Council for Research (IBB-CNR), Area di Ricerca Site and Headquarters, Via Pietro Castellino 111, 80131 Naples, ItalyIn recent years, fungal infections have emerged as a significant health concern across veterinary species, especially in livestock such as cattle, where fungal diseases can result in considerable economic losses, as well as in humans. In particular, <i>Aspergillus</i> species, notably <i>Aspergillus flavus</i> and <i>Aspergillus versicolor</i>, are opportunistic pathogens that pose a threat to both animals and humans. This study focuses on the synthesis and antifungal evaluation of novel 9-fluorenylmethoxycarbonyl (Fmoc)-protected 1,2,4-triazolyl-α-amino acids and their dipeptides, designed to combat fungal pathogens. More in detail, we evaluated their antifungal activity against various species, including <i>Aspergillus versicolor</i> (ATCC 12134) and <i>Aspergillus flavus</i> (ATCC 10567). The results indicated that dipeptide <b>7a</b> exhibited promising antifungal activity against <i>Aspergillus versicolor</i> with an IC<sub>50</sub> value of 169.94 µM, demonstrating greater potency than fluconazole, a standard treatment for fungal infections, which showed an IC<sub>50</sub> of 254.01 µM. Notably, dipeptide <b>7a</b> showed slightly enhanced antifungal efficacy compared to fluconazole also in <i>Aspergillus flavus</i> (IC<sub>50</sub> 176.69 µM vs. 184.64 µM), suggesting that this dipeptide might be more potent even against this strain. Remarkably, <b>3a</b> and <b>7a</b> are also more potent than fluconazole against <i>A. candidus</i> 10711. On the other hand, the protected amino acid <b>3a</b> demonstrated consistent inhibition across all tested <i>Aspergillus</i> strains, but with an IC<sub>50</sub> value of 267.86 µM for <i>Aspergillus flavus</i>, it was less potent than fluconazole (IC<sub>50</sub> 184.64 µM), still showing some potential as a good antifungal molecule. Overall, our findings indicate that the synthesized 1,2,4-triazolyl derivatives <b>3a</b> and <b>7a</b> hold significant promise as potential antifungal agents in treating <i>Aspergillus</i>-induced diseases in cattle, as well as for broader applications in human health. Our mechanistic studies based on molecular docking revealed that compounds <b>3a</b> and <b>7a</b> bind to the same region of the sterol 14-α demethylase as fluconazole. Given the rising concerns about antifungal resistance, these amino acid derivatives, with their unique bioactive structures, could serve as a novel class of therapeutic agents. Further research into their in vivo efficacy and safety profiles is warranted to fully realize their potential as antifungal drugs in clinical and agricultural settings.https://www.mdpi.com/2218-273X/15/1/611,2,4-triazolesantifungal peptidessynthesisdipeptidesfluconazolenon-protein amino acids |
| spellingShingle | Tatevik Sargsyan Lala Stepanyan Henrik Panosyan Heghine Hakobyan Monika Israyelyan Avetis Tsaturyan Nelli Hovhannisyan Caterina Vicidomini Anna Mkrtchyan Ashot Saghyan Giovanni N. Roviello Synthesis and Antifungal Activity of Fmoc-Protected 1,2,4-Triazolyl-α-Amino Acids and Their Dipeptides Against <i>Aspergillus</i> Species Biomolecules 1,2,4-triazoles antifungal peptides synthesis dipeptides fluconazole non-protein amino acids |
| title | Synthesis and Antifungal Activity of Fmoc-Protected 1,2,4-Triazolyl-α-Amino Acids and Their Dipeptides Against <i>Aspergillus</i> Species |
| title_full | Synthesis and Antifungal Activity of Fmoc-Protected 1,2,4-Triazolyl-α-Amino Acids and Their Dipeptides Against <i>Aspergillus</i> Species |
| title_fullStr | Synthesis and Antifungal Activity of Fmoc-Protected 1,2,4-Triazolyl-α-Amino Acids and Their Dipeptides Against <i>Aspergillus</i> Species |
| title_full_unstemmed | Synthesis and Antifungal Activity of Fmoc-Protected 1,2,4-Triazolyl-α-Amino Acids and Their Dipeptides Against <i>Aspergillus</i> Species |
| title_short | Synthesis and Antifungal Activity of Fmoc-Protected 1,2,4-Triazolyl-α-Amino Acids and Their Dipeptides Against <i>Aspergillus</i> Species |
| title_sort | synthesis and antifungal activity of fmoc protected 1 2 4 triazolyl α amino acids and their dipeptides against i aspergillus i species |
| topic | 1,2,4-triazoles antifungal peptides synthesis dipeptides fluconazole non-protein amino acids |
| url | https://www.mdpi.com/2218-273X/15/1/61 |
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