TY - JOUR
T1 - Curcumin derivatives as metal-chelating agents with potential multifunctional activity for pharmaceutical applications
AU - Ferrari, Erika
AU - Benassi, Rois
AU - Sacchi, Stefania
AU - Pignedoli, Francesca
AU - Asti, Mattia
AU - Saladini, Monica
PY - 2014
Y1 - 2014
N2 - Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimer's disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga 3 +, Cu2 +) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto-enol form. The formation of metal complexes is followed by both NMR and UV-vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga3 + and Cu2 + are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O) 2]+ was found more stable than curcumin one. Good agreement is detected between calculated and experimental 1H and 13C NMR data. The calculated OH bond dissociation energy (BDE) and the OH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga3 + complexes display possible superoxide dismutase (SOD)-like activity.
AB - Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimer's disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga 3 +, Cu2 +) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto-enol form. The formation of metal complexes is followed by both NMR and UV-vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga3 + and Cu2 + are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O) 2]+ was found more stable than curcumin one. Good agreement is detected between calculated and experimental 1H and 13C NMR data. The calculated OH bond dissociation energy (BDE) and the OH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga3 + complexes display possible superoxide dismutase (SOD)-like activity.
KW - Alzheimer's disease
KW - Curcumin derivatives
KW - DFT calculation
KW - NMR spectroscopy
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U2 - 10.1016/j.jinorgbio.2014.06.002
DO - 10.1016/j.jinorgbio.2014.06.002
M3 - Article
C2 - 24968097
AN - SCOPUS:84903307085
VL - 139
SP - 38
EP - 48
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
SN - 0162-0134
ER -