Cytochalasins from the Ash Endophytic Fungus <i>Nemania diffusa</i> DSM 116299
The secondary metabolome of <i>Nemania diffusa</i>, isolated as an ash endophytic fungus, was analyzed in detail. From its cultures, a previously undescribed cytochalasin <b>1</b> was isolated using preparative HPLC, together with six known congeners: 18-dehydroxy-cytochalasi...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/4/957 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850080999551008768 |
|---|---|
| author | Özge Demir Katharina Schmidt Barbara Schulz Theresia E. B. Stradal Frank Surup |
| author_facet | Özge Demir Katharina Schmidt Barbara Schulz Theresia E. B. Stradal Frank Surup |
| author_sort | Özge Demir |
| collection | DOAJ |
| description | The secondary metabolome of <i>Nemania diffusa</i>, isolated as an ash endophytic fungus, was analyzed in detail. From its cultures, a previously undescribed cytochalasin <b>1</b> was isolated using preparative HPLC, together with six known congeners: 18-dehydroxy-cytochalasin E (<b>2</b>), cytochalasins Z<sub>7</sub> (<b>3</b>), Z<sub>8</sub> (<b>4</b>), and E (<b>5</b>), 18-dehydroxy-17-didehydro-cytochalasin E (<b>6</b>), and K Steyn (<b>7</b>). The structures of these compounds were determined using data from high-resolution mass spectrometry (HR-MS), in combination with 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. Metabolites <b>1</b>–<b>4</b> share a characteristic 12-membered lactone moiety, placing them within a rarely examined cytochalasin subclass. Thus, the compounds were incorporated into our ongoing screening campaign to study the structure–activity relationship of this metabolite family. We initially determined their cytotoxicity in eukaryotic mouse fibroblast L929 cells using an MTT-based colorimetric assay, and further investigated their effect on the cellular actin dynamics of the human osteosarcoma cell line U-2OS in detail. Unexpectedly, we discovered a high number of irreversible compounds (<b>1</b>, <b>2</b>, and <b>4</b>). Additionally, we highlighted specific structural features within the 12-membered cytochalasin subclass that may play a role in directing the reversibility of these compounds. |
| format | Article |
| id | doaj-art-b0187215d28544bca4961175c8c552e8 |
| institution | DOAJ |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-b0187215d28544bca4961175c8c552e82025-08-20T02:44:50ZengMDPI AGMolecules1420-30492025-02-0130495710.3390/molecules30040957Cytochalasins from the Ash Endophytic Fungus <i>Nemania diffusa</i> DSM 116299Özge Demir0Katharina Schmidt1Barbara Schulz2Theresia E. B. Stradal3Frank Surup4Department of Microbial Drugs, Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyDepartment of Cell Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyInstitute of Microbiology, Technical University of Braunschweig, 38106 Braunschweig, GermanyDepartment of Cell Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyDepartment of Microbial Drugs, Helmholtz Centre for Infection Research, 38124 Braunschweig, GermanyThe secondary metabolome of <i>Nemania diffusa</i>, isolated as an ash endophytic fungus, was analyzed in detail. From its cultures, a previously undescribed cytochalasin <b>1</b> was isolated using preparative HPLC, together with six known congeners: 18-dehydroxy-cytochalasin E (<b>2</b>), cytochalasins Z<sub>7</sub> (<b>3</b>), Z<sub>8</sub> (<b>4</b>), and E (<b>5</b>), 18-dehydroxy-17-didehydro-cytochalasin E (<b>6</b>), and K Steyn (<b>7</b>). The structures of these compounds were determined using data from high-resolution mass spectrometry (HR-MS), in combination with 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. Metabolites <b>1</b>–<b>4</b> share a characteristic 12-membered lactone moiety, placing them within a rarely examined cytochalasin subclass. Thus, the compounds were incorporated into our ongoing screening campaign to study the structure–activity relationship of this metabolite family. We initially determined their cytotoxicity in eukaryotic mouse fibroblast L929 cells using an MTT-based colorimetric assay, and further investigated their effect on the cellular actin dynamics of the human osteosarcoma cell line U-2OS in detail. Unexpectedly, we discovered a high number of irreversible compounds (<b>1</b>, <b>2</b>, and <b>4</b>). Additionally, we highlighted specific structural features within the 12-membered cytochalasin subclass that may play a role in directing the reversibility of these compounds.https://www.mdpi.com/1420-3049/30/4/957fungal endophytessecondary metabolitesstructure elucidationcytotoxicityactin inhibitors |
| spellingShingle | Özge Demir Katharina Schmidt Barbara Schulz Theresia E. B. Stradal Frank Surup Cytochalasins from the Ash Endophytic Fungus <i>Nemania diffusa</i> DSM 116299 Molecules fungal endophytes secondary metabolites structure elucidation cytotoxicity actin inhibitors |
| title | Cytochalasins from the Ash Endophytic Fungus <i>Nemania diffusa</i> DSM 116299 |
| title_full | Cytochalasins from the Ash Endophytic Fungus <i>Nemania diffusa</i> DSM 116299 |
| title_fullStr | Cytochalasins from the Ash Endophytic Fungus <i>Nemania diffusa</i> DSM 116299 |
| title_full_unstemmed | Cytochalasins from the Ash Endophytic Fungus <i>Nemania diffusa</i> DSM 116299 |
| title_short | Cytochalasins from the Ash Endophytic Fungus <i>Nemania diffusa</i> DSM 116299 |
| title_sort | cytochalasins from the ash endophytic fungus i nemania diffusa i dsm 116299 |
| topic | fungal endophytes secondary metabolites structure elucidation cytotoxicity actin inhibitors |
| url | https://www.mdpi.com/1420-3049/30/4/957 |
| work_keys_str_mv | AT ozgedemir cytochalasinsfromtheashendophyticfungusinemaniadiffusaidsm116299 AT katharinaschmidt cytochalasinsfromtheashendophyticfungusinemaniadiffusaidsm116299 AT barbaraschulz cytochalasinsfromtheashendophyticfungusinemaniadiffusaidsm116299 AT theresiaebstradal cytochalasinsfromtheashendophyticfungusinemaniadiffusaidsm116299 AT franksurup cytochalasinsfromtheashendophyticfungusinemaniadiffusaidsm116299 |