Alkaloid-Based Therapeutics in Cancer Biology

Alkaloids comprise a vast class of naturally occurring, nitrogen-containing compounds produced by plants, fungi and certain marine organisms. Since the mid-20th century, several alkaloid derivatives—such as camptothecin analogues and vinca alkaloids—have become mainstays of chemotherapy, owing to their potent interference with DNA replication, microtubule dynamics and cell-cycle regulation. Advances in analytical chemistry and high-throughput screening have expanded the known repertoire of anti-cancer alkaloids to tens of thousands of structurally diverse molecules, many of which act through apoptosis induction, topoisomerase inhibition, epigenetic modulation or disruption of tumour microenvironment signalling. Contemporary efforts now combine synthetic biology, metabolic engineering and heterologous expression to scale the production of complex alkaloid scaffolds in microbial or plant chassis, while structural modification and semi-synthesis aim to enhance selectivity and reduce systemic toxicity. Parallel investigations explore alkaloid-based radiosensitisers and radioprotectors that can improve therapeutic index in combination with radiotherapy. Globally, these natural products continue to inspire drug discovery pipelines, offering opportunities to address drug resistance and to develop novel multi-targeted regimens against diverse cancer types.

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Alkaloid-Based Therapeutics in Cancer Biology publication trend

The graph below shows the total number of articles in alkaloid-based therapeutics in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Alkaloid: A naturally occurring organic compound containing one or more nitrogen atoms, often with potent pharmacological effects.

De novo synthesis: Biosynthetic assembly of complex molecules from simple precursors within a living organism or engineered system.

Heterologous expression: Expression of a gene or pathway in a non-native host organism to enable production of a desired metabolite.

Cytotoxicity: The capacity of a substance to kill or inhibit the growth of cells, commonly measured in vitro against cancer cell lines.

Indole nucleus: A bicyclic chemical structure formed by a benzene ring fused to a five-membered nitrogen-containing pyrrole ring, common in many bioactive alkaloids.

References

1. Current Status and De Novo Synthesis of Anti-Tumor Alkaloids in Nicotiana. Metabolites (2023).
2. Diversity in Chemical Structures and Biological Properties of Plant Alkaloids. Molecules (2021).
3. New cytotoxic indole-type alkaloids obtained from Rhazya stricta leaves. South African Journal of Botany (2021).
4. Skeleton Synthesis of a Plant-Derived Radioprotective Alkaloid Born to Produce a Novel Fused Heterocycle. Molecules (2023).
5. Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms. Molecules (2017).