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

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 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.