title: Exploring pyrimidine-substituted curcumin analogues: design, synthesis and effects on EGFR signaling.
abstract: Epidermal growth factor receptor (EGFR) is an effective molecular target of anti-cancer therapies. Curcumin inhibits cancer cell growth in vitro by suppressing gene expression of EGFR and reduces tumor growth in various animal models. To overcome instable and insoluble properties of curcumin as therapeutics, we designed and synthesized six novel pyrimidine-substituted curcumin analogues with or without a hydroxyl group originally present in curcumin. The cell viability tests indicated that IC50 of the analogues containing hydroxyl group were 3 to 8-fold lower than those of the analogues without hydroxyl group in two colon cancer cell lines tested. Western blot analysis indicates the analogues containing hydroxyl group inhibited expression and tyrosine phosphorylation of EGFR. Further protein analyses showed that the analogues had anti-cellular proliferation, pro-apoptosis, and cell cycle arrest properties associated with suppressed EGFR expression. These results indicate that the hydroxyl groups in curcumin and the analogues were critical for observed biological activities.
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors.forename: Peiju
authors.initials: P
authors.lastname: Qiu
authors.forename: Lingling
authors.initials: L
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Shixi
authors.initials: S
authors.lastname: Wang
authors.forename: Sheng
authors.initials: S
authors.lastname: Tong
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011743:Pyrimidines / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D011743:Pyrimidines; D066246:ErbB Receptors; D003474:Curcumin; C030986:pyrimidine
keywords: Apoptosis; Cell cycle; Colon cancer; Curcumin analogues; EGFR