Send to

Choose Destination
Bioorg Med Chem. 2015 Apr 1;23(7):1507-1514. doi: 10.1016/j.bmc.2015.02.003. Epub 2015 Feb 13.

Novel curcumin analogs to overcome EGFR-TKI lung adenocarcinoma drug resistance and reduce EGFR-TKI-induced GI adverse effects.

Author information

Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA.
Hokkaido Pharmaceutical University, School of Pharmacy, 7-1, Katsuraoka-cho, Otaru 047-02, Japan.
Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
School of Pharmacy, China Medical University, Taichung, Taiwan.
Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
Contributed equally


Curcumin (1) down-regulates the expression as well as phosphorylation of epidermal growth factor receptor (EGFR) in lung adenocarcinoma cells expressing gefitinib-resistant EGFR. Thirty-seven newly synthesized curcumin analogues including dimethoxycurcumin (2, DMC) were evaluated for their effects on EGFR expression as well as phosphorylation in two gefitinib-resistant lung adenocarcinoma cell lines, CL1-5 (EGFR(wt)) and H1975 (EGFR(L858R+T790M)). Based on the identified structure-activity relationships, methoxy substitution at C-3', C-4', or both positions favored inhibitory activity (compounds 1, 2, 5, 8-15, 17, 36), while compounds with more polar substituents were generally less active in both cell lines. Compound 36 with a fluorine substituent at C-6' and its protonated counterpart 2 did not lose activity, suggesting halogen tolerance. In addition, a conjugated linker was essential for activity. Among all evaluated curcumin derivatives, compound 2 showed the best inhibitory effects on both wild-type and mutant EGFR by efficiently inducing gefitinib-insensitive EGFR degradation. Compound 23 also reduced gefitinib-induced gastrointestinal damage in the non-transformed intestinal epithelial cell line IEC-18.


Curcumin; EGFR; Gastrointestinal tract; Lung adenocarcinoma; Tyrosine kinase inhibitor

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center