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Redox Disruption Induced by Saquayamycin B1 Promotes Cytotoxicity in Resistant Melanoma Cells

Geovana Guedes Silvestre1, Thalisson Amorim de Souza1, Alan Ferreira Alves1

  • 1Postgraduate Program of Bioactives Natural and Synthetics Products, PgPNSB, Federal University of Paraíba, João Pessoa, Brazil.

Chemmedchem
|May 22, 2026
PubMed

Insights

Saquayamycin B1, an angucycline, shows potent antimelanoma activity by disrupting cellular redox balance. This compound effectively targets key redox regulators, offering a promising avenue for treating chemoresistant melanoma.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • Melanoma is an aggressive skin cancer with limited treatment success due to rapid progression and chemoresistance.
  • Targeting redox pathways presents a potential strategy to overcome therapeutic limitations in melanoma.

Purpose of the Study:

  • To investigate the antimelanoma activity of Saquayamycin B1 (SQ-B1), an angucycline.
  • To elucidate the mechanism of SQ-B1's action, focusing on its impact on cellular redox balance.

Main Methods:

  • Purification of SQ-B1 from Streptomyces sp. I072 via M9 fermentation and chromatography.
  • Structure elucidation using 1D/2D NMR and mass spectrometry.
  • Cytotoxicity assays (MTT) on human melanoma cell lines (SK-MEL-5, -113, -117, -134).
  • Assessment of reactive oxygen species (ROS) and glutathione levels.
  • Molecular docking and dynamics simulations to identify target proteins.

Main Results:

  • SQ-B1 exhibited significant cytotoxicity against melanoma cells with IC50 values ranging from 0.99 to 5.01 μM.
  • N-acetylcysteine (NAC) pretreatment rescued cell viability, confirming a ROS-dependent mechanism.
  • SQ-B1 treatment decreased the GSH/GSSG ratio and increased superoxide (O2•−) and nitric oxide (NO•) levels, indicating oxidative stress.
  • Molecular docking predicted strong binding of SQ-B1 to glutathione transferase (GSTP1-1) and glutathione reductase (GSR).
  • Molecular dynamics confirmed stable interactions between SQ-B1 and GSR.

Conclusions:

  • SQ-B1 induces melanoma cell cytotoxicity by disrupting the cellular redox balance.
  • The compound effectively targets key redox-regulating enzymes like GSR.
  • SQ-B1 demonstrates potential as a novel redox-modulating therapeutic agent for chemoresistant melanoma.
Keywords:
Streptomycesangucyclineselectronic paramagnetic resonance (EPR)glutathione S‐transferase pi 1‐1 (GSTP1‐1)oxidative stress

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