Naphthoquinone Chemistry in Cancer Therapeutics

Naphthoquinones are a class of bicyclic quinones characterised by conjugated carbonyl moieties and a planar aromatic scaffold. Both natural and synthetic derivatives have attracted interest as anticancer agents owing to their ability to engage in redox cycling, generate reactive oxygen species (ROS) and form covalent adducts with cellular nucleophiles. These mechanisms converge on mitochondrial dysfunction, DNA damage and perturbation of redox‐sensitive signalling pathways, leading to cell‐cycle arrest and apoptosis in malignant cells. Structural modifications—such as alkyl, amino or chalcogen substituents—can fine-tune redox potential, lipophilicity and selectivity for tumour versus normal tissue. Recent work has explored sustainable synthetic protocols for both 1,4- and 1,2-naphthoquinone cores, while advances in molecular docking and electrochemical analysis have provided mechanistic insights that guide rational design. Collectively, these efforts underscore the global significance of naphthoquinone scaffolds as leads for next-generation chemotherapeutics with the potential to overcome drug resistance and target diverse tumour types.

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Naphthoquinone Chemistry in Cancer Therapeutics publication trend

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Technical terms

1,4-Naphthoquinone: A quinone isomer with carbonyl groups at positions 1 and 4 of the naphthalene ring, often serving as a redox-active core.

1,2-Naphthoquinone: A less common isomer with adjacent carbonyl groups at positions 1 and 2, which can alter redox potential and reactivity.

Redox cycling: A process in which a compound undergoes repeated reduction and oxidation, generating ROS that can damage cellular components.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can induce oxidative stress and trigger cell death pathways.

Apoptosis: Programmed cell death characterised by nuclear fragmentation, membrane blebbing and biochemical signalling.

Cell-cycle arrest: Inhibition of cell division at specific checkpoints, preventing tumour proliferation.

IC₅₀: The concentration of a compound required to inhibit a biological process by 50%, commonly used to assess cytotoxic potency.

Structure–activity relationship (SAR): The relationship between chemical structure and biological activity, guiding modification of lead compounds.

References

1. The Relevance and Insights on 1,4-Naphthoquinones as Antimicrobial and Antitumoral Molecules: A Systematic Review. Pharmaceuticals (2023).
2. Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone Derivatives. Molecules (2023).
3. The diverse mechanisms and anticancer potential of naphthoquinones. Cancer Cell International (2019).