Discovery of novel anti-tumor curcumin analogues from the optimization of curcumin scaffold
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A series of novel curcumin analogues were synthesized by optimization of its aromatic ring. The antiproliferative activities of these analogues were screened against four human cancer cell lines by MTT assay and some displayed significant improvement in antiproliferative activity compared with curcumin. The most potent compound 10 exhibited antiproliferative activity against Caco-2, Bel-7402, MDA-MB-231, and DU145 cancer cells with IC50 values of 2.04, 1.54, 4.99, and 3.22 μM, respectively. Annexin V/propidium iodide double staining and flow cytometry cell cycle analysis using propidium iodide DNA staining revealed that compound 10 induced apoptosis and cell cycle arrest at G1 phase in Bel-7402 cells in a dose-dependent manner. Moreover, in an in vivo mouse model of liver cancer xenograft, compound 10 substantially inhibited liver tumor growth at a dose of 20 mg/kg/day without observable toxic effect.
KeywordsCurcumin Optimization Antitumor Apoptosis
This work was supported by grants from the National Program on Key Basic Research Project (973 Program, No. 2011CB504405), the National Natural Scientific Foundation of China (No. 81372121, 81572146), and the Key Project of Shanghai Science and Technology Commission (No. 13411951002).
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Conflict of interest
The authors declare that they have no competing interests.
- Mahran RI, Hagras MM, Sun D, Brenner DE (2016) Bringing curcumin to the clinic in cancer prevention: a review of strategies to enhance bioavailability and efficacy. AAPS J. doi: 10.1208/s12248-016-0003-2
- Makarov MV, Yu E, Anikina RV, Pukhov SA, Klochkov SG, Mischenko DV, Neganova ME, Khrustalev VN, Klemenkova ZS, Brel VK (2016) 1,5-Diaryl-3-oxo-1,4-pentadienes based on (4-oxopiperidin-1-yl)(aryl) methyl phosphonate scaffold: synthesis and antitumor properties. Med Chem Res. doi: 10.1007/s00044-016-1726-4
- Teymouri M, Barati N, Pirro M, Sahebkar A (2016) Biological and pharmacological evaluation of dimethoxycurcumin: a metabolically stable curcumin analogue with a promising therapeutic potential. J Cell Physiol. doi: 10.1002/jcp.25749.
- Yu S, Wang X, He X, Wang Y, Gao S, Ren L, Shi Y (2016) Curcumin exerts anti-inflammatory and antioxidative properties in 1-methyl-4-phenylpyridinium ion (MPP(+))-stimulated mesencephalic astrocytes by interference with TLR4 and downstream signaling pathway. Cell Stress Chaperones 21:697–705CrossRefPubMedPubMedCentralGoogle Scholar