Natural Product Bioactivity Profiling Techniques

Natural products continue to serve as a rich source of pharmacologically active molecules, necessitating robust profiling methods to link chemical diversity to biological function. Contemporary bioactivity profiling techniques integrate high‐resolution enzyme inhibition assays with advanced separation and spectroscopic platforms, allowing researchers to localise active constituents within complex mixtures. Bioactivity‐guided fractionation employs parallel detection of biological activity alongside chromatographic separation, streamlining the identification of bioactive peaks. Hyphenated systems such as HPLC‐HRMS‐SPE‐NMR merge liquid chromatography with high‐resolution mass spectrometry, solid‐phase extraction and nuclear magnetic resonance to expedite structural elucidation. Label‐free cell‐based assays, including high‐content imaging, reveal phenotypic changes and suggest mechanisms of action. Recent advances in microfluidic devices and automation have reduced sample consumption and increased throughput, while computational docking and data‐integration tools support target annotation and interaction prediction. Together, these approaches accelerate the progression from crude extracts to lead compounds, underpinning efforts against antimicrobial resistance, metabolic disorders and cancer.

Research from Nature Portfolio

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Research from all publishers

Recent work has demonstrated the power of high‐resolution enzyme inhibition profiling in natural product discovery. One study applied high‐resolution profiling to protein tyrosine phosphatase 1B, integrating detailed kinetics and molecular docking to identify and characterise novel diterpenoid inhibitors with distinct modes of action. Another investigation combined HPLC‐HRMS‐SPE‐NMR with α‐glucosidase inhibition assays to pinpoint and elucidate potent antidiabetic compounds from a complex botanical extract, illustrating how hyphenated platforms accelerate structural annotation. A further report employed dual high‐resolution profiling of both protein tyrosine phosphatase 1B and α‐glucosidase, coupled with LC‐PDA‐HRMS and chiral separations, to discover unprecedented coumarin–chromone scaffolds, expanding the repertoire of leads for metabolic disease targets. These examples highlight the synergy of bioassays and advanced analytical technologies in driving forward natural product research.

Natural Product Bioactivity Profiling Techniques publication trend

The graph below shows the total number of articles in natural product bioactivity profiling techniques across all publications each year (not limited to Nature Index journals).

Technical terms

High‐resolution bioactivity profiling: An approach combining fine‐scale chromatographic separation with concurrent activity assays to localise bioactive molecules within mixtures.

HPLC‐HRMS‐SPE‐NMR: A hyphenated workflow coupling high‐performance liquid chromatography, high‐resolution mass spectrometry, solid‐phase extraction and nuclear magnetic resonance for rapid compound separation and structure determination.

LC‐PDA‐HRMS: Liquid chromatography with photodiode array detection and high‐resolution mass spectrometry for comprehensive compound profiling and identification.

Protein tyrosine phosphatase 1B (PTP1B): An enzyme that modulates insulin signalling and represents a therapeutic target in metabolic disorders.

α‐Glucosidase: A carbohydrate‐hydrolysing enzyme whose inhibition delays dietary glucose absorption and is exploited in diabetes management.

References

1. Identification of new PTP1B-inhibiting decipiene diterpenoid esters from Eremophila clarkei by high-resolution PTP1B inhibition profiling, enzyme kinetics analysis, and molecular docking. Bioorganic Chemistry (2023).
2. High-Resolution α-Glucosidase Inhibition Profiling Combined with HPLC-HRMS-SPE-NMR for Identification of Antidiabetic Compounds in Eremanthus crotonoides (Asteraceae). Molecules (2016).