Polypharmacology-Labeled Molecular Networking: An Analytical Technology Workflow for Accelerated Identification of...

Area of Science:

• Natural product chemistry
• Analytical chemistry
• Pharmacology

Background:

• Emerging pandemics necessitate sustainable drug discovery from natural sources.
• Exploring Nature's chemical space requires advanced analytical technologies.

Purpose of the Study:

• To introduce polypharmacology-labeled molecular networking (PLMN) for efficient identification of bioactive compounds in complex extracts.
• To apply PLMN to discover antihyperglycemic and antibacterial constituents from Eremophila rugosa.

Main Methods:

• Utilized merged positive and negative ionization tandem mass spectrometry-based molecular networking.
• Integrated polypharmacological high-resolution inhibition profiling.
• Analyzed Eremophila rugosa crude extract using the PLMN workflow.

Main Results:

• Identified 27 novel non-canonical nerylneryl diphosphate-derived diterpenoids.
• Discovered serrulatane ferulate esters with antihyperglycemic and antibacterial activities.
• Observed synergistic antibacterial activity against MRSA and specific binding to protein-tyrosine phosphatase 1B.

Conclusions:

• PLMN facilitates rapid and comprehensive analysis of bioactive natural products.
• Eremophila rugosa contains promising compounds for drug discovery, particularly for metabolic and infectious diseases.
• PLMN offers a scalable approach, potentially revolutionizing natural product-based drug discovery.