1,720,969 research outputs found
Fe(III) containing complexes with beta-diketo derivatives for treatment of iron deficiency
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Development of new therapeutic Metal(III)-chelating agents derived from Curcumin
No full textWith the aim to develop new anti-cancer approaches, which encompass therapies based on drug combinations, we are searching for innovative anti-tumor multi-targets treatments.1 In this research Curcumin represents our referring and starting point for the design of new derivatives. Curcumin, a natural occurring molecule, was shown to inhibit growth of several types of malignant cells and its biological activity was also related to its iron chelating ability.2,3 Recently curcumin proceeded onto clinical trials however its use is limited by a poor stability and bioavailability. In order to improve these features, we have synthesized new derivatives which potentially conjugate anti-proliferative and anti-oxidant effects with metal chelating capacity, especially towards Fe(III) and Ga(III), reducing free iron level and potentially delivering a chemotherapic metal ion such as Ga(III). We have performed a complete characterization of the chelating ability of new ligands in vitro by means of potentiometry, UV-Vis spectroscopy and NMR spectrometry. Stability and cellular uptake together with cytotoxicity towards different cell lines were also investigated for all ligands and their Ga(III) complexes in order to shed light on their potential anti-cancer effects especially against human colon cancer cells, unravelling the molecular basis of their biological activity
New 99mTc(I) and Re(I) Curcumin derivatives for molecular imaging
No full textRe(I) complexs with curcumin is here discusse
Solvent effect on keto-enol tautomerism in a new B-diketone: a comparison between experimental data and different theoretical approaches.
No full textThe novel -diketo compound (3-acetyl-4-oxopentanoic acid) OPAA is here synthesized, completely characterized in the solid state by means of X-ray crystallography and in solution by potentiometry and 1H and 13C NMR spectroscopy. In the solid state, OPAA exhibits the di-keto (DK) structure, while in solution a strongly solvent dependent tautomeric equilibrium is observed. Theoretical ab-initio calculations employing DFT at B3LYP/6-311G** level and different methods of theoretical model chemistry (CBS-4M, G3MP2, CBS-QB3) are used to extensively investigate the tautomeric equilibrium in comparison with experimental data. Solvent effects are evaluated using CPCM continuum solvation method; among all implied methods, CBS-4M is the one that better predicts experimental data and is able to qualitatively describe tautomeric equilibrium in solution, allowing thermodynamic calculation of pKa. Furthermore a supermolecular solvent approach is used to better analyze solvent-solute interactions in order to forecast chemical properties
Development of new metal-chelating multi target drus derived from Curcumin
No full textWith the aim to develop new anti-cancer approaches, which encompass therapies based on drug combinations, we are searching for innovative anti-tumor multi-targets treatments.1 In this research Curcumin represents our referring and starting point for the design of new derivatives. Curcumin, a natural occurring molecule, was shown to inhibit growth of several types of malignant cells and its biological activity was also related to its iron chelating ability.2 Recently curcumin proceeded onto clinical trials however its use is limited by a poor bioavailability. In order to improve curcumin water solubility and drug-delivery we have synthesized new derivatives which conjugate anti-proliferative effects with metal chelating capacity. They are able to reduce free iron level and to potentially deliver a chemotherapic metal ion such as Ga(III)
Development of new metal-based phyto-radiopharmaceuticals: diagnostic agents derived from Cur(e)cumin
No full textCurcumin, a yellow pigment extracted from the Indian spice Curcuma longa, has been widely linked with suppression of angiogenesis, inflammation, cardiovascular diseases, tumorigenesis and A-binding activities in the context of therapies for Alzheimer’s disease [1,2].
Besides, Curcumin has shown interesting binding ability towards different metal ions such as Fe(III) and Ga(III) with the involvement of its keto-enolic moiety [3]. Metal complexation triggers an increased kinetic stability and bioavailability of Curcumin in physiological conditions, reducing one of its main drawbacks in therapeutic applications.
Anyway biologically active curcuminoids have little been investigated as labelled radiopharmaceuticals for cancer diagnosis or therapy, and they represent a novelty in the field.
In this presentation we show an overview of new classes of Curcumin-based ligands with bidentate and tridentate coordinating mode, we investigate their binding ability towards Rhenium and Gallium and report a complete thermodynamic and pharmaco-kinetic study on ligands and metal complexes with the aim of developing new radiopharmaceuticals
Synthesis, cytotoxic and combined cDDP activity of new stable curcumin derivatives
No full textNew curcumin derivatives are synthesized in order to improve chemical properties of curcumin. The aromatic ring glycosylation of curcumin provides more water-soluble compounds with a greater kinetic stability which is a fundamental feature for drug bioavailability. The glycosylation reaction is quite simple, low cost, with high yield and minimum waste. NMR data show that the ability of curcumin to coordinate metal ion, in particular Ga(III), is maintained in the synthesized products. Although the binding of glucose to curcumin reduces the cytotoxicity of the derivatives towards cisplatin (cDDP)-sensitive and -resistant human ovarian carcinoma cell lines, the compounds display a good selectivity since they are much less toxic against non-tumourigenic Vero cells. The combination of cDDP with the most active glycosyl-curcuminoid drug against both cDDP-sensitive and -resistant as well as against Vero cell lines is tested. The results show an improvement of cDDP efficacy with higher selectivity towards cancer cells than non-cancer cells. These studies indicate the need for developing new valid components of drug treatment protocols to cDDP-resistant cells as well
Curcumin derivatives as metal-chelating agents with potential multifunctional activity for pharmaceutical applications
No full textCurcuminoids 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 (Ga3 +, 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 Osingle bondH bond dissociation energy (BDE) and the Osingle bondH 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
Understanding the molecular mechanisms of Curcumin derivatives chemotherapic activity
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Curcumin derivatives: molecular basis of their anti-cancer activity.
No full textCurcumin, a phenolic compound from the plant Curcuma longa L., has shown a wide-spectrum of chemopreventive, anti-oxidant and anti-tumor properties. Although its promising chemotherapeutic activity, preclinical and clinical studies highlight Curcumin limited therapeutic application due to its instability in physiological conditions. To improve its stability and activity, many derivatives have been synthesized and studied, among which bis-DemethoxyCurcumin (bDMC) and diAcetylCurcumin (DAC). In this report, we show that both bDMC and DAC are more stable than Curcumin in physiological medium. To explore the mechanism of their chemotherapeutic effect, we studied their role in proliferation in the HCT116 human colon cancer cells. We correlated kinetic stability and cellular uptake data to their biological effects. Both bDMC and DAC impair correct spindles formation and induce a p53- and p21(CIP1/WAF1)- independent mitotic arrest, which is more stable and long-lasting for bDMC. A subsequent p53/p21(CIP1/WAF1)- dependent inhibition of G1 to S transition is triggered by Curcumin and DAC as a consequence of the mitotic slippage, preventing postmitotic cells from re-entering the cell cycle. Conversely, the G1/S arrest induced by bDMC is a direct effect of the drug and concomitant to the mitotic block. Finally, we demonstrate that bDMC induces rapid DNA double-strand breaks, moving for its possible development in anti-cancer clinical applications
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