Applying molecular networking for targeted isolation of depsipeptides

Area of Science:

• Natural Product Chemistry
• Microbiology
• Pharmacology

Background:

• Streptomyces conglobatus RJ8 is a source of bioactive secondary metabolites.
• Neoantimycins (NATs) are a class of natural products with potential therapeutic applications.

Purpose of the Study:

• To isolate and characterize new neoantimycin analogs from Streptomyces conglobatus RJ8.
• To investigate the cytotoxic activity of the isolated compounds against human carcinoma cell lines.

Main Methods:

• Liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) molecular networking for targeted isolation.
• Chemical derivatization and hydrolysis for absolute structure determination.
• Cytotoxicity assays using multiple human carcinoma cell lines.

Main Results:

• Three new neoantimycin analogs (1, 3, 5) and two known analogs (2, 4) were isolated.
• Compounds 2/3 and 4/5 were identified as epimeric pairs, a novel finding for NATs.
• Compound 1 and its derivative 6 demonstrated excellent cytotoxicity (picomolar IC50) against six human carcinoma cell lines.
• Compounds 7 and 8 showed potent cytotoxicity against PC-9 and PC-9/GR cell lines.

Conclusions:

• The study successfully isolated and characterized novel neoantimycin analogs and their epimers.
• The isolated compounds, particularly 1 and 6, exhibit significant cytotoxic potential, warranting further investigation for cancer therapy.