Evaluation of a quercetin–gadolinium complex as an efficient positive contrast enhancer for magnetic resonance imaging

Abstract

The need for a highly effective contrast agent that aids in distinguishing normal and affected cells is in great demand in clinics for accurate diagnosis. In this context, the present study attempts to utilize the metal ion complexation capacity of a pharmacologically relevant dietary flavonol, quercetin for development of a novel MRI contrast agent. The flavonoidmetal complex was synthesized using quercetin dihydrate and gadolinium acetate and characterized by elemental analysis, spectroscopy techniques, thermal analysis and powder XRD. The quercetin: gadolinium stoichiometry was determined to be 1:1 using Job's Plot analysis and the equilibrium stability constant of metal binding to quercetin determined from fluorimetric analysis using Stern-Volmer equations indicated excellent stability. The magnetic properties of the complex were typical of a paramagnetic material as confirmed using vibrating sample magnetometry. The antioxidant property of the quercetin-gadolinium complex was greater than that of its parent ligand when evaluated by DPPH assay due to the structural changes. Cyclic voltammetry studies of both quercetin and its gadolinium complex was performed to confirm complexation and its anti-oxidant potential. The viability of cancer cells, MCF7 and normal L929 cells remained unaffected after exposure to the complex. The efficacy of this complex as a positive contrast agent in MRI was evaluated using Phantom agar gel assay and in vitro studies. It was found to exhibit superior positive contrast when compared with the commercially available contrast agent. This complex therefore may be evaluated further as a novel MR contrast agent for pre-clinical and clinical applications. 41.470 nm respectively. The diffraction pattern of the complex was indexed by standard methods and the (h k l) values were calculated using DICVOL91 software 48 . Comparison of the results (Tables 2A & 2B), reveals that there was good agreement between the values of 2θ and d values and it correlates the literature information 49 . Using dichotomy method, the unit cell of reduced volume was obtained and the direct cell parameters of QGd complex were found to be A = 8.9469(0.012)Å, B = 3.7877(0.004)Å, C = 7.646(0.020) Å and β = 104.517(0.100)° corresponding to a monoclinic system. Similar formation of monoclinic systems have been reported in literature for heteronuclear complexes of Ln 3+ -Fe 3+ and Ln 3+ -Co 3+ complexes (Ln: lanthanide) that were bridged by cyanide moieties 50 and lanthanide complexes with 3-hydroxypicolinic acid 51 .Figure 3. Powder X-ray diffractogram for Q and QGd complex

Differential Effects of Quercetin and Two of Its Derivatives, Isorhamnetin and Isorhamnetin-3-glucuronide, in Inhibiting the Proliferation of Human Breast-Cancer MCF-7 Cells

“…Furthermore, some other studies have showed that Que has strong anticancer effect on a wide range of cancer cells such as acute lymphoid, myeloid leukemia cells, human gastric and colon cancer cells. [7][8][9][10][11] It is also reported that Que, IS and I3G have high antioxidant ability, 34 23,37 It must be noted that the concentrations (25, 50 and 100 μM) we used in this study may generally be not physiological and achievable in vivo because of the low bioavailability of these compounds. In this study we mainly investigated the anticancer-structure relationships between Que, IS and I3G in vitro and try to provide the foundation for high bioavailability and water solubility metabolites of quercetin in vivo evaluation, and to evaluate the potential clinical use of this study.…”

“…5,6 As one of the primary flavonoids, quercetin (3,3′,4′,5,7-pentahydroxyflavone) has been reported to have anti-tumor effect on many tumor cells, which may be related to catechol moiety in B ring and free hydroxyl groups in the quercetin structure. [7][8][9][10][11] Recent studies have showed that quercetin can be metabolized into various sulphated, glucuronidated and methylated forms in different organs, such as liver, kidney, colon and small intestine, and its metabolites may still act as antioxidants with higher hydrophily. 12 Our previous studies have also showed that QS (quercetin-5',8-disulfonate) can possess remarkably high anti-tumor activity in human breast cancer MCF-7 cells, 11 indicating that sulfated metabolites of quercetin may play an important role in cytotoxic effects.…”

Vanadium rutin complex sensitizes breast cancer cells via modulation of p53/Bax/Bcl2/VEGF correlated with apoptotic events

“…The results acquired from the cell viability studies and oligonucleosomal fragmentation by DAPI staining indicated that the vanadium-rutin complex diminishes cell proliferation and encourages apoptosis both MCF-7 and MDA-MB-231 cells. One of the fundamental characteristics of anticancer agents is their capability to regulate cell cycle and which is achieved through the arrest of G1 and G2 phases (47). The style of apoptosis induced by vanadium-rutin complex was established by flow cytometric analysis using FITC tagged Annexin-V and PI staining.…”

A Novel Ruthenium Fluvastatin Complex Downregulates SNCG Expression to Modulate Breast Carcinoma Cell Proliferation and Apoptosis Via Activating PI3K/Akt/mTOR/VEGF/ MAP Kinase Pathway

“…MTT assay showed that complex ruthenium uvastatin can minimize cell proliferation and induce apoptosis. One of most important purposes of anticancer therapies is the modulation of the cell cycle, speci cally the inhibition of phases G1 and G2 plays a key role in the cell cycle cascade (84). To determine the complex's mechanistic approach to the induction of apoptosis, ow cytometric experiments were employed that made use of Annexin-V and PI staining procedures.…”