Synthesis and Bioactivity of Chromone Derivatives

Chromones, characterised by a benzopyranone core, constitute a versatile heterocyclic scaffold widely exploited in medicinal and materials chemistry. Synthetic strategies span classical base-catalysed cyclodehydration of β-diketones, transition-metal-mediated cross-couplings and domino cyclisations of enaminones. Recent emphasis has fallen on green and sustainable protocols, including solvent-free mechanochemical methods and microwave-assisted transformations, which afford structural diversity with reduced environmental impact. Structure–activity relationship studies reveal that substitution at the 3- and 2-positions modulates electronic properties and target affinity, yielding derivatives with notable anticancer, anti-inflammatory and antimicrobial profiles. Advances in catalytic methodologies and reagent design have enabled access to acylated, styryl and pyrazole-fused chromones, broadening the chemical space for lead discovery. Bioactivity evaluations demonstrate that fine-tuning of substituents can enhance tumour specificity and minimise off-target toxicity, underscoring the scaffold’s global significance in drug design, agrochemicals and functional materials.

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Synthesis and Bioactivity of Chromone Derivatives publication trend

The graph below shows the total number of articles in synthesis and bioactivity of chromone derivatives across all publications each year (not limited to Nature Index journals).

Technical terms

Chromone: A benzopyranone scaffold featuring a fused benzene and α-pyrone ring, central to numerous bioactive compounds.

Mechanochemical synthesis: A solvent-free technique in which mechanical force (e.g., grinding) drives chemical reactions, often enhancing efficiency and sustainability.

Nanocellulose: Nano-sized cellulose fibrils used as a biodegradable and renewable reaction medium or catalyst support in green chemistry.

Acylation: Introduction of an acyl group (R–C=O) into a molecule, commonly employed to modify pharmacophore properties.

Tumour specificity: The selective cytotoxicity of a compound toward cancer cells over non-malignant cells, crucial for reducing side effects in chemotherapy.

Microwave-assisted organic synthesis: Use of microwave irradiation to heat chemical reactions rapidly and uniformly, improving reaction rates, yields and selectivity.

References

1. Nanocellulose as Convenient Reaction Media for the FeCl3 Mediated Mechanochemical Synthesis of 3‑Acylchromones. ACS Sustainable Chemistry & Engineering (2023).
2. New Entries to 3‐Acylchromones: TM‐Catalysed Decarboxylative Cross‐Coupling of α‐Keto Acids with ortho‐Hydroxyarylenaminones, 2,3‐Unsubstituted Chromones and 3‐Iodochromones. European Journal of Organic Chemistry (2018).
3. Synthesis of (E)-2-Styrylchromones and Flavones by Base-Catalyzed Cyclodehydration of the Appropriate β-Diketones Using Water as Solvent. Molecules (2015).
4. Synthesis of Chromone-Related Pyrazole Compounds. Molecules (2017).
5. Microwave Irradiation: Alternative Heating Process for the Synthesis of Biologically Applicable Chromones, Quinolones, and Their Precursors. Molecules (2021).
6. Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma. Medicines (2020).