Natural Product Synthesis and Biological Activity in Cancer Therapy

Natural products have long served as a rich reservoir for anticancer drug discovery, offering structural complexity and unique mechanisms of action. Advances in synthetic chemistry—including total synthesis, late-stage functionalisation, biocatalysis and combinatorial biosynthesis—now permit the efficient assembly and diversification of intricate molecular scaffolds derived from plants, marine organisms and microorganisms. Parallel progress in high-throughput screening and cell-based assays has sharpened structure–activity relationship studies, enabling the rational design of analogues with improved solubility, stability and selectivity. Key therapeutic strategies include targeting microtubule dynamics, protein synthesis machinery, signalling kinases and epigenetic regulators, as well as inducing apoptosis and inhibiting angiogenesis. Together, synthetic innovations and biological evaluation foster the translation of natural leads into clinically valuable anticancer agents, addressing drug resistance and expanding global treatment options.

Research from Nature Portfolio

Recent work has introduced photoaffinity pyrene-based probes for macrolide antitumour agents, which, upon light activation, form covalent adducts with cytoskeletal targets. Label-assisted laser desorption/ionisation mass spectrometry of these probes has revealed detailed ligand–protein interaction patterns, guiding the synthesis of more potent macrolide analogues and advancing our understanding of natural product binding modes in cancer cells.

Natural Product Synthesis and Biological Activity in Cancer Therapy publication trend

The graph below shows the total number of articles in natural product synthesis and biological activity in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Photoredox catalysis: A strategy that employs light-activated catalysts to drive single-electron transfer reactions, enabling selective functionalisation of complex molecules.

Photoaffinity probe: A chemical tool bearing a photoreactive group that, upon irradiation, covalently links to target proteins for mapping binding sites and mode-of-action studies.

Gem-dimethylation: The installation of two methyl groups on the same carbon atom to modulate the pharmacokinetic and pharmacodynamic properties of a compound.

Structure–activity relationship (SAR): The systematic analysis of how variations in molecular structure influence biological activity, guiding the optimisation of lead compounds.

Eukaryotic elongation factor 1A (eEF1A): A translation-related protein that delivers aminoacyl-tRNA to the ribosome and serves as a target for diverse anticancer natural products.

References

1. Photoredox-catalyzed reaction as a powerful tool for rapid natural product Gem-dimethylation modification: discovery of potent anti-cancer agents with improved druggability. Acta Materia Medica (2023).
2. Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art. International Journal of Molecular Sciences (2023).
3. 6-Amidopyrene as a label-assisted laser desorption/ionization (LA-LDI) enhancing tag: development of photoaffinity pyrene derivative. Scientific Reports (2015).