Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures

Area of Science:

• Natural Product Chemistry
• Drug Discovery
• Biochemistry

Background:

• Natural products offer diverse molecules for drug screening.
• Identifying active compounds in complex mixtures is challenging and time-consuming.

Purpose of the Study:

• To develop a novel platform for probing the pharmacological potential of natural products.
• To identify bioactive compounds in dietary supplements using a cell affinity assay and computational analysis.

Main Methods:

• Shotgun derivatization of natural product extracts with isotopically labeled propanoic acid.
• Live cell affinity assay using HeLa cells to identify compounds with high cell binding.
• Computational liquid chromatography-mass spectrometry (LC-MS) analysis of derivatized compounds from cell lysate.

Main Results:

• Hundreds of compounds were derivatized, with dozens showing high affinity for HeLa cells.
• Over a thousand isotopically labeled compounds were screened, identifying known bioactive compounds and six new structures.
• Discovered three tulsinol compounds from Ocimum tenuiflorum and three novel valeraninium alkaloids from Valeriana officinalis.

Conclusions:

• The developed 'tag and snag' workflow is a viable method for natural product drug discovery.
• The newly identified valeraninium alkaloids represent a distinct class with potential for novel bioactivity.