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Review

A perspective on the chemical structures and molecular mechanisms of curcumin and its derivatives and analogs in cancer treatment (Review)

  • Authors:
    • Lujie Zhu
    • Yanghan Wang
    • Qilin Wang
  • View Affiliations / Copyright

    Affiliations: Shandong Key Laboratory of Applied Technology for Protein and Peptide Drugs, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng, Shandong 252059, P.R. China, Department of Biological Science, College of Agriculture and Biology, Liaocheng University, Liaocheng, Shandong 252059, P.R. China
  • Article Number: 75
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    Published online on: August 1, 2025
       https://doi.org/10.3892/ijo.2025.5782
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Abstract

Curcumin is a polyphenolic nutraceutical compound, which has a variety of pharmacological properties that may prevent or treat cancer, chronic inflammation, depression, anxiety and nerve damage. However, due to the poor solubility of curcumin in water and instability, it has limited applications. Therefore, a series of curcumin derivatives or analogs have been designed and synthesized to optimize the physicochemical and therapeutic properties and pharmacokinetic features of curcumin. Curcumin derivatives or analogs have been shown to possess beneficial biochemical effects, thus have been considered as potential medications. The present review summarized the structural characteristics and classification of available curcumin derivatives or analogs, and described the molecular mechanisms of curcumin and its derivatives as potential pharmaceutical drugs in various types of cancer, such as lung, prostate, breast and colorectal cancer. The present review also discussed the adverse effects and limitations of curcumin and its derivatives/analogs in preclinical and clinical trials. Analysis of the existing studies on curcumin may potentially contribute to the design and synthesis of innovative curcumin derivatives or analogs as drugs and tools in therapeutic, preventative and diagnostic medical applications in associated diseases.
View Figures

Figure 1

Molecular structures of ketone and
enol structures of curcumin. (A) Ketone and (B) enol. Under
alkaline conditions, the presence of two phenolic hydroxyl groups
at the ends of the molecular structure makes it prone to
conjugation, resulting in keto-enol tautomerism.

Figure 2

Molecular structures of curcuminoids.
(A) Demethoxycurcumin, (B) bisdemethoxycurcumin and (C)
cyclocurcumin.

Figure 3

Molecular structures of
demethylcurcumin and bisdemethylcurcumin. (A) Demethylcurcumin and
(B) bisdemethylcurcumin are the two main forms of curcumin
metabolized in the body. In contrast to curcumin, demethylcurcumin
and bisdemethylcurcumin are formed due to one or two methyl groups
on the hydroxyl oxygens on the aryl rings being replaced by
hydrogen, respectively.

Figure 4

Hydrogenated curcumin derivatives.
(A) Tetrahydrocurcumin, (B) hexahydrocurcumin and (C)
octahydrocurcumin. These three hydrogenated curcumins are the
metabolites of curcumin in the liver as well as in the intestinal
mucosa by phase I metabolism.

Figure 5

Halogenated curcumin derivative.
Phenolic hydroxyl groups on curcumin are replaced by halogens,
where X represents F, Cl or Br.

Figure 6

Dimethylaminomethyl curcumin
derivative. The methoxy group on one acyl ring is replaced by
dimethylaminomethyl, which increases the water solubility of the
curcumin derivative and the steric hindrance of the molecule to
protect the active phenolic hydroxyl group.

Figure 7

Monocarbonyl-modified compound. This
monocarbonyl curcumin analog has only one keto group in the
aliphatic chain, which makes its water solubility higher and more
stable.

Figure 8

Bis-imino and bis-amino curcumin
derivatives. (A) Bis-amino curcumin and (B) Bis-imino curcumin.

Figure 9

Aliphatic chain-modified substituent.
The carbon 4 atom between the β-diketones of curcumin is linked to
aromatic aldehydes with two phenolic hydroxyl groups.

Figure 10

Modified diketone derivative. In the
structure, the carbon-oxygen double bonds (carbonyl group) of
curcumin in the long unsaturated aliphatic chain are replaced with
carbon- nitrogen bonds.

Figure 11

Curcumin-piperlongumine hybrid
molecule. The curcumin-piperlongumine hybrid molecule is
synthesized using a molecular hybridization strategy based on the
structure of curcumin and piperlongumine, which reduces the
instability of the chemical structure of curcumin and the toxic
side effects of piperlongumine.

Figure 12

Curcumin metal-chelating derivative.
Curcumin is coordinated with the metal aluminum to form a
metal-chelating derivative.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu L, Wang Y and Wang Q: A perspective on the chemical structures and molecular mechanisms of curcumin and its derivatives and analogs in cancer treatment (Review). Int J Oncol 67: 75, 2025.
APA
Zhu, L., Wang, Y., & Wang, Q. (2025). A perspective on the chemical structures and molecular mechanisms of curcumin and its derivatives and analogs in cancer treatment (Review). International Journal of Oncology, 67, 75. https://doi.org/10.3892/ijo.2025.5782
MLA
Zhu, L., Wang, Y., Wang, Q."A perspective on the chemical structures and molecular mechanisms of curcumin and its derivatives and analogs in cancer treatment (Review)". International Journal of Oncology 67.3 (2025): 75.
Chicago
Zhu, L., Wang, Y., Wang, Q."A perspective on the chemical structures and molecular mechanisms of curcumin and its derivatives and analogs in cancer treatment (Review)". International Journal of Oncology 67, no. 3 (2025): 75. https://doi.org/10.3892/ijo.2025.5782
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu L, Wang Y and Wang Q: A perspective on the chemical structures and molecular mechanisms of curcumin and its derivatives and analogs in cancer treatment (Review). Int J Oncol 67: 75, 2025.
APA
Zhu, L., Wang, Y., & Wang, Q. (2025). A perspective on the chemical structures and molecular mechanisms of curcumin and its derivatives and analogs in cancer treatment (Review). International Journal of Oncology, 67, 75. https://doi.org/10.3892/ijo.2025.5782
MLA
Zhu, L., Wang, Y., Wang, Q."A perspective on the chemical structures and molecular mechanisms of curcumin and its derivatives and analogs in cancer treatment (Review)". International Journal of Oncology 67.3 (2025): 75.
Chicago
Zhu, L., Wang, Y., Wang, Q."A perspective on the chemical structures and molecular mechanisms of curcumin and its derivatives and analogs in cancer treatment (Review)". International Journal of Oncology 67, no. 3 (2025): 75. https://doi.org/10.3892/ijo.2025.5782
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