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Background/Objectives: Some specific anthraquinone derivatives (AQs) are known to be used widely as effective chemotherapeutic agents in the treatment of cancer. However, their fundamental shortcoming is the high rate of cardiotoxicity observed in treated patients, which is thought to be caused by the increase in production of reactive oxygen species (ROS) catalyzed by iron and copper. The development of improved AQs and other anticancer drugs with enhanced efficacy but reduced toxicity remains a high priority. The aim of this study was to evaluate the cytotoxic and ROS production effects of chelate iron and copper complexes of two novel AQs, namely 4-hydroxynaphto[2,3-h]cinnoline-7,12-dione (Q2) and 3-(hydroxymethyl)naphto[2,3-h]cinnoline-4,7,12(1H)-trione (Q3). Methods: The chelation ability of Q2 and Q3 was studied using NMR and UV–Vis spectroscopy. Cytotoxicity studies were carried out using the MTT assay. The influence of chelation on ROS production was studied using NMR spectroscopy in linoleic acid micelles. Results: It was found that only Q3 forms complexes with Fe(III) and Cu(II) ions, whereas Q2 does not demonstrate chelating properties. A cytotoxicity study revealed that Fe[Q3]3 significantly decreased the viability of lung cancer A549 cells, while Q3 and Cu[Q3]2 did not demonstrate cytotoxic properties in this cell line. Furthermore, the presence of Q3 lowered the rate of iron-induced lipid peroxidation in linoleic acid micelles. By contrast, Q2 did not influence the rate of lipid peroxidation, probably due to the absence of effective metal chelating ability. Conclusions: The high cytotoxic effects observed with the iron complex of Q3 against cancer cells in combination with a reduced rate of iron induced lipid peroxidation in the presence of Q3, make Q3 and its iron complex promising for further evaluation and use as chemotherapeutic agents in cancer. [ABSTRACT FROM AUTHOR]

Crocin is a unique water-soluble carotenoid found in crocus and gardenia flowers. Crocin has been shown to have a variety of pharmacological activities, such as antioxidant, anti-cancer, memory improvement, antidepressant, anti-ischemia, blood pressure lowering and aphrodisiac, gene protection and detoxification activities. Due to their amphiphilicity, crocin molecules form concentration-dependent self-associates (micelles) in a water solution. In the present study, using various NMR techniques (T2 relaxation and selective gradient NOESY), we have demonstrated that crocin forms mixed micelles with water-soluble drug delivery system glycyrrhizin and linoleic acid molecules. Note, that the spin–spin T2 relaxation time and NOESY spectroscopy are very sensitive to intermolecular interactions and molecular diffusion mobility. The second purpose of this work was the elucidation of the interaction of crocin with a model lipid membrane using NMR techniques and a molecular dynamics simulation and its effects on lipid oxidation. It was shown that the crocin molecule is located near the surface of the lipid bilayer and effectively protects lipids from oxidation by peroxyl radicals. The role of glycyrrhizin and vitamin C in metal-induced lipid oxidation was also elucidated. The results of this study may be useful for expanding the field of application of crocin in medicine and in the food industry. [ABSTRACT FROM AUTHOR]

The sensitivity of Ho–phospholipid complexes to changes in the membrane viscosity of liposomes was checked. An increase in viscosity was observed for DPPC and DMPC near the phase-transition temperature. Ho–phospholipid complexes could be used as sensors of local membrane viscosity in NMR and MRI technologies. [ABSTRACT FROM AUTHOR]

The role of metal ions in the mechanism of light-stimulated redox activity of potential anticancer agent 2-phenyl-4-(butylamino)naphtha[2,3-h]quinoline-7,12-dione (Qc) has been studied by CIDNP (chemically induced dynamic nuclear polarization) and EPR methods. The photo-induced oxidation of NADH and its synthetic analog - substituted dihydropyridine (DHP) - by quinone Qc was used as a model. The Qc capability of producing chelating complexes with divalent metal ions of Fe, Zn and Ca was studied quantitatively by optical absorption spectroscopy. A significant decrease of electrochemical reduction potential of Qc (Δ E=0.4−0.6 eV for ACN and ACN/PBS solutions) in chelating complexes and in protonated form of Qc was observed. A pronounced increase in efficiency of DHP oxidation in chelating complexes with Zn2+ and Ca2+ ions compared with free Qc was demonstrated. The yields of free radicals, including reactive oxygen species (ROS) and reaction products, were a few times higher than those in the absence of metal ions. Application of such chelating compounds to enhance ROS generation looks very promising for anti-cancer therapy, including the photodynamic therapy. [ABSTRACT FROM AUTHOR]

The peculiarities of spin effects in photoinduced electron transfer (ET) in diastereomers of donor-acceptor dyads are considered in order to study the influence of chirality on reactivity. Thus, the spin selectivity—the difference between the enhancement coefficients of chemically induced dynamic nuclear polarization (CIDNP)—of the dyad's diastereomers reflects the difference in the spin density distribution in its paramagnetic precursors that appears upon UV irradiation. In addition, the CIDNP coefficient itself has demonstrated a high sensitivity to the change of chiral centers: when one center is changed, the hyperpolarization of all polarized nuclei of the molecule is affected. The article analyzes the experimental values of spin selectivity based on CIDNP calculations and molecular dynamic modeling data in order to reveal the effect of optical configuration on the structure and reactivity of diastereomers. In this way, we succeeded in tracing the differences in dyads with L- and D-tryptophan as an electron donor. Since the replacement of L-amino acid with D-analog in specific proteins is believed to be the cause of Alzheimer's and Parkinson's diseases, spin effects and molecular dynamic simulation in model dyads can be a useful tool for investigating the nature of this phenomenon. [ABSTRACT FROM AUTHOR]