Redox Disruption Induced by Saquayamycin B1 Promotes Cytotoxicity in Resistant Melanoma Cells
Fuente:
Wiley Open Access
Salvato in:
| Autori principali: | , , , , , , , , , , , , , |
|---|---|
| Natura: | Artículo Open Access |
| Pubblicazione: |
Wiley
2026
|
| Soggetti: | |
| Accesso online: | |
| Tags: |
Aggiungi Tag
Nessun Tag, puoi essere il primo ad aggiungerne!!
|
| _version_ | 1867002639283126272 |
|---|---|
| author | Geovana Guedes Silvestre Thalisson Amorim de Souza Alan Ferreira Alves Valeria Dutan‐Patiño Jean‐Michel Huvelin Mathilde Gourdel Mikael Croyal Samuel Cibulski Demetrius Antonio Machado de Araújo Marcus Tullius Scotti Josean Fechine Tavares Angela Tesse El‐Hassan Nazih Marianna Vieira Sobral |
| author_facet | Geovana Guedes Silvestre Thalisson Amorim de Souza Alan Ferreira Alves Valeria Dutan‐Patiño Jean‐Michel Huvelin Mathilde Gourdel Mikael Croyal Samuel Cibulski Demetrius Antonio Machado de Araújo Marcus Tullius Scotti Josean Fechine Tavares Angela Tesse El‐Hassan Nazih Marianna Vieira Sobral Geovana Guedes Silvestre Thalisson Amorim de Souza Alan Ferreira Alves Valeria Dutan‐Patiño Jean‐Michel Huvelin Mathilde Gourdel Mikael Croyal Samuel Cibulski Demetrius Antonio Machado de Araújo Marcus Tullius Scotti Josean Fechine Tavares Angela Tesse El‐Hassan Nazih Marianna Vieira Sobral |
| collection | Wiley Open Access |
| contents | Redox Disruption Induced by Saquayamycin B1 Promotes Cytotoxicity in Resistant Melanoma Cells Geovana Guedes Silvestre Thalisson Amorim de Souza Alan Ferreira Alves Valeria Dutan‐Patiño Jean‐Michel Huvelin Mathilde Gourdel Mikael Croyal Samuel Cibulski Demetrius Antonio Machado de Araújo Marcus Tullius Scotti Josean Fechine Tavares Angela Tesse El‐Hassan Nazih Marianna Vieira Sobral ChemMedChem Melanoma is an aggressive skin cancer characterized by rapid progression and frequent chemoresistance, which limits the success of current therapies. Saquayamycin B1 (SQ‐B1), an angucycline isolated from Streptomyces sp. I072, was investigated for its antimelanoma activity with emphasis on redox disruption. The compound was purified using M9 fermentation followed by semipreparative liquid chromatography, and its structure was confirmed through 1D/2D nuclear magnetic resonance (NMR) and mass spectrometry. Cytotoxicity assays (MTT, 72 h) in SK‐MEL‐5, −113, −117, and −134 cells revealed IC 50 values between 5.01 and 0.99 μM. Pretreatment with N‐acetylcysteine (NAC) rescued cell viability at IC 50 and sub‐IC 50 concentrations, supporting a ROS‐dependent mechanism. SQ‐B1 (4 μM, 24 h) reduced the GSH/GSSG ratio (3.49 ± 0.70 vs. 12.35 ± 0.27 in controls) and increased O 2•− and NO • levels, indicating marked oxidative imbalance. Molecular docking suggested strong binding of SQ‐B1 to glutathione transferase (GSTP1‐1; p ≈ 0.86) and glutathione reductase (GSR; p ≈ 0.97), with weaker affinity for GPx4 ( p ≈ 0.35). Molecular dynamics confirmed stable interactions between SQ‐B1 and GSR (RMSD plateau ~10 ns) with a total interaction energy of −201.0 kJ/mol. These findings indicate that SQ‐B1 induces cytotoxicity through targeting of key redox regulators, highlighting its potential as a redox‐modulating candidate for chemoresistant melanoma. 10.1002/cmdc.70308 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/cmdc.70308 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_cmdc_70308 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2026 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Redox Disruption Induced by Saquayamycin B1 Promotes Cytotoxicity in Resistant Melanoma Cells Geovana Guedes Silvestre Thalisson Amorim de Souza Alan Ferreira Alves Valeria Dutan‐Patiño Jean‐Michel Huvelin Mathilde Gourdel Mikael Croyal Samuel Cibulski Demetrius Antonio Machado de Araújo Marcus Tullius Scotti Josean Fechine Tavares Angela Tesse El‐Hassan Nazih Marianna Vieira Sobral ChemMedChem Redox Disruption Induced by Saquayamycin B1 Promotes Cytotoxicity in Resistant Melanoma Cells Geovana Guedes Silvestre Thalisson Amorim de Souza Alan Ferreira Alves Valeria Dutan‐Patiño Jean‐Michel Huvelin Mathilde Gourdel Mikael Croyal Samuel Cibulski Demetrius Antonio Machado de Araújo Marcus Tullius Scotti Josean Fechine Tavares Angela Tesse El‐Hassan Nazih Marianna Vieira Sobral ChemMedChem Melanoma is an aggressive skin cancer characterized by rapid progression and frequent chemoresistance, which limits the success of current therapies. Saquayamycin B1 (SQ‐B1), an angucycline isolated from Streptomyces sp. I072, was investigated for its antimelanoma activity with emphasis on redox disruption. The compound was purified using M9 fermentation followed by semipreparative liquid chromatography, and its structure was confirmed through 1D/2D nuclear magnetic resonance (NMR) and mass spectrometry. Cytotoxicity assays (MTT, 72 h) in SK‐MEL‐5, −113, −117, and −134 cells revealed IC 50 values between 5.01 and 0.99 μM. Pretreatment with N‐acetylcysteine (NAC) rescued cell viability at IC 50 and sub‐IC 50 concentrations, supporting a ROS‐dependent mechanism. SQ‐B1 (4 μM, 24 h) reduced the GSH/GSSG ratio (3.49 ± 0.70 vs. 12.35 ± 0.27 in controls) and increased O 2•− and NO • levels, indicating marked oxidative imbalance. Molecular docking suggested strong binding of SQ‐B1 to glutathione transferase (GSTP1‐1; p ≈ 0.86) and glutathione reductase (GSR; p ≈ 0.97), with weaker affinity for GPx4 ( p ≈ 0.35). Molecular dynamics confirmed stable interactions between SQ‐B1 and GSR (RMSD plateau ~10 ns) with a total interaction energy of −201.0 kJ/mol. These findings indicate that SQ‐B1 induces cytotoxicity through targeting of key redox regulators, highlighting its potential as a redox‐modulating candidate for chemoresistant melanoma. 10.1002/cmdc.70308 http://creativecommons.org/licenses/by/4.0/ |
| title | Redox Disruption Induced by Saquayamycin B1 Promotes Cytotoxicity in Resistant Melanoma Cells |
| topic | ChemMedChem |
| url | https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.70308 |