Molecular Networking-Guided Discovery of a New Antitumor Pyranonaphthoquinone from Streptomyces tanashiensis DSM 731: Insights from Single-Molecule Stretching Assays

Chembiochem. 2025 Jan 14;26(2):e202400732. doi: 10.1002/cbic.202400732. Epub 2024 Nov 6.

Abstract

Guided by molecular networking based on single-molecule stretching assay, an unprecedented pyranonaphthoquinone, methyl kalafunginate (1) and five known compounds 2-6 were isolated from Streptomyces tanashiensis DSM 731. Compound 1 was characterized through a combination of spectroscopic techniques, including 1D and 2D NMR analysis, ECD calculation, and X-ray crystallography. Interestingly, we discovered that compound 1 was spontaneously converted from kalafungin (4) in methanol solution. All isolated compounds, except for compound 3, were assessed for their cytotoxic potential against a panel of five human cancer cell lines: A549, HepG2, BxPC-3, SW620, and C4-2B. Compounds 1, 2, 4, and 5 exhibited remarkable cytotoxicity with IC50 values below 2.382 μM, suggesting their potential as promising anticancer agents. These findings highlight the significance of using a combined approach of single-molecule stretching assays and molecular networking for efficiently discovering novel natural products with potential therapeutic applications.

Keywords: Cytotoxicity; Molecular networking; Natural product; Non-enzymatic reaction; Pyranonaphthoquinone.

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / isolation & purification
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Drug Discovery*
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Naphthoquinones* / chemistry
  • Naphthoquinones* / isolation & purification
  • Naphthoquinones* / pharmacology
  • Pyrans* / chemistry
  • Pyrans* / isolation & purification
  • Pyrans* / pharmacology
  • Streptomyces* / chemistry
  • Streptomyces* / metabolism

Substances

  • Naphthoquinones
  • Antineoplastic Agents
  • Pyrans