title: Synthesis of novel curcuminoids accommodating a central β-enaminone motif and their impact on cell growth and oxidative stress.
abstract: Curcuminoids are high-potential drugs targeting multiple components of vital signaling pathways without being toxic, and are therefore considered to be valuable lead structures in medicinal chemistry. Unfortunately, most curcuminoids poorly reach their site of action because of low bioavailability issues, (partly) associated with the labile β-diketo structure. In that respect, curcumin derivatives bearing a central β-enaminone fragment may have improved solubility and intestinal stability, and therefore may represent a new class of analogs with higher bioactivity. In that mindset, thirteen N-alkyl enaminones were efficiently synthesized via a novel approach, using montmorillonite K10 clay and microwave irradiation. These compounds were then characterized in terms of solubility and chemical anti-oxidant properties, and were applied in screening assays for cell toxicity, growth and oxidative stress using CHO-K1, EA.hy926, HT-29 and Caco-2 cell lines. Compared to native curcumin, many nitrogen derivatives showed a stronger antiproliferative effect, which was highly structure and cell type dependent. In addition, the correlation between cell viability and reactive oxygen species production was limited. Therefore, this set of novel curcumin derivatives may be useful to unravel other mechanisms of oxidative stress-related diseases, and eventually be used as more bioavailable and bioactive alternatives for native curcumin.
authors: SynBioC Research Group, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000, Ghent, Belgium.
authors: Rob
authors: R
authors: De Vreese
authors: Department of Food Safety and Food Quality, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000, Ghent, Belgium.
authors: Charlotte
authors: C
authors: Grootaert
authors: Department of Food Safety and Food Quality, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000, Ghent, Belgium.
authors: Sander
authors: S
authors: D'hoore
authors: SynBioC Research Group, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000, Ghent, Belgium.
authors: Atiruj
authors: A
authors: Theppawong
authors: SynBioC Research Group, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000, Ghent, Belgium.
authors: Sam
authors: S
authors: Van Damme
authors: SynBioC Research Group, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000, Ghent, Belgium.
authors: Maarten
authors: M
authors: Van Bogaert
authors: Department of Food Safety and Food Quality, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000, Ghent, Belgium. Electronic address: John.VanCamp@UGent.be.
authors: John
authors: J
authors: Van Camp
authors: SynBioC Research Group, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000, Ghent, Belgium. Electronic address: matthias.dhooghe@UGent.be.
authors: Matthias
authors: M
authors: D'hooghe
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003412:Cricetulus; D003474:Curcumin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D012995:Solubility
chemical_list: D000975:Antioxidants; D003474:Curcumin
keywords: Curcumin; Cytotoxicity; Oxidative stress; Synthesis; β-enaminones