What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

Stilbenes are naturally occurring phytoalexins that generally exist as their more stable E isomers. The most well known natural stilbene is resveratrol (Res), firstly isolated in 1939 from roots of Veratrum grandiflorum (white hellebore) (1) and since then found in various edible plants, notably in Vitis vinifera L. (Vitaceae) (2). The therapeutic potential of Res covers a wide range of diseases, and multiple beneficial effects on human health such as antioxidant, anti-inflammatory and anti-cancer activities have been suggested based on several in vitro and animal studies (3). In particular, Res has been reported to be an inhibitor of carcinogenesis at multiple stages via its ability to inhibit cyclooxygenase, and is an anticancer agent with a role in antiangiogenesis (4). Moreover, both in vitro and in vivo studies showed that Res induces cell cycle arrest and apoptosis in tumor cells (4). However, clinical studies in humans evidenced that Res is rapidly absorbed after oral intake, and that the low level observed in the blood stream is caused by a fast conversion into metabolites that are readily excreted from the body (5). Thus, considerable efforts have gone in the design and synthesis of Res analogues with enhanced metabolic stability. Considering that reduced Res (dihydro- resveratrol, D-Res) conjugates may account for as much as 50% of an oral Res dose (5), and that D-Res has a strong proliferative effect on hormone-sensitive cancer cell lines such as breast cancer cell line MCF7 (6), we recently devoted our synthetic efforts to the preparation of trans-restricted analogues of Res in which the E carbon-carbon double bond is embedded into an imidazole nucleus. To keep the trans geometry, the two aryl rings were linked to the heteroaromatic core in a 1,3 fashion. Based on this design, we successfully prepared a variety of 1,4-, 2,4- and 2,5-diaryl substituted imidazoles including Res analogues 1, 2 and 3, respectively, by procedures that involve transition metal-catalyzed Suzuki-Miyaura cross-coupling reactions and highly selective N-H or C-H direct arylation reactions as key synthetic steps. The anticancer activity of compounds 1–3 was evaluated against the 60 human cancer cell lines panel of the National Cancer Institute (NCI, USA). The obtained results, that will be showed and discussed along with the protocols developed for the preparation of imidazoles 1–3, confirmed that a structural optimization of Res may provide analogues with improved potency in inhibiting the growth of human cancer cell lines in vitro when compared to their natural lead. (1) Takaoka,M.J.Chem.Soc.Jpn.1939,60,1090-1100. (2) Langcake, P.; Pryce, R. J. Physiological. Plant Patology 1976, 9, 77-86. (3) Vang, O.; et al. PLoS ONE 2011, 6, e19881. doi:10.1371/journal.pone.0019881 (4) Kraft, T. E.; et al. Critical Reviews in Food Science and Nutrition 2009, 49, 782-799. (5) Walle, T. Ann. N.Y. Acad. Sci. 2011, 1215, 9-15. doi: 10.1111/j.1749-6632.2010.05842.x (6) Gakh,A.A.;etal.Bioorg.Med.Chem.Lett.2010,20,6149-6151

2-Hydroxy-3-methoxymethyl-5-methylbenzaldehyde

In the title molecule, C10H12O3, all non-H atoms lie in a common plane (r.m.s deviation = 0.010 Å). The molecular conformation is stabilized by an intramolecular O—H...O hydrogen bond

Synthesis, spectral and electrochemical studies of novel porphyrin bound tetranuclear acyclic manganese(III) and copper(II) complexes

9-15The tetranucleating manganese(III) and copper(II) complexes of the type Mn4LP2, Cu4LP2, where H6LP2= 1,4 bis[2'-hydroxy-3'-(iminotetraphenylporphyrin)-5'-methylbenzyl] piperazine, were synthesized and characterized. Mn4LP2 complex is EPR silent and this indicates that manganese is in +3 oxidation state. Cu4LP2 complex shows broad band with g value centered at 2.06 indicates antiferromagnetic coupling. Cyclic voltammetry studies indicating that the Mn4LP2 complex undergoes quasireversible electron transfer in the cathodic potential region and irreversible electron transfer in the anodic potential region. Cu4LP2 complex undergoes irreversible electron transfer in the cathodic potential region, quasireversible electron transfer in the anodic potential region

Epoxidation of olefin using Mn(III) tetraphenylporphyrin complex as catalyst

505-509Manganese(III) tetraphenylporphyrin acetate (Mn(III)(TPP)OAc) has been synthesized and characterised by C, H,N analysis, IR and electronic spectra. The electrochemical studies of the complex show a single quasireversible electron transfer process at Epc = 0.620 V. Polyisoprene and polychloroprene were epoxidized using Mn(TPP)OAc complex as catalyst and NaOCl or PhIO as oxygen donor. Both polyisoprene and polychloroprene were epoxidized completely within 7 h using NaOCl as oxygen donors and in 12 h using PhIO as the oxygen donor. The reaction was monitored by IR spectroscopy. The peak at 1020 cm-1 due to -CH=CH- disappears completely and a peak has been observed at 970 cm-1, characteristic of oxiranes, indicating the complete conversion of the polyene to polyepoxide. Cyclohexene and styrene were epoxidised using Mn(TPP)OAc complex as catalyst and NaOCl and PhIO as oxygen donors.Epoxidation of styrene is complete in 30 min with 100% yield of styrene epoxide using PhIO, whereas it takes 1h for the completion of the reaction using NaOCl and gives mixed products with 59.71% styrene epoxide, 21.89% benzaldehyde and 18.40% phenylacetaldehyde. Epoxidation of cyclohexene is complete in 1 h using NaOCl with 33.57% cyclohexeneoxide, 13.01% of cyclohex-2-ene-1-ol and 53.42% of cyclohex-2-ene-1-one, whereas the reaction was only 31.22% completed in 1 h using PhIO with 22.06% yield of 2-cyclohexeneoxide, 4.23% of cyclohex-2-ene-1-ol and 4.93% of cyclohex-2-ene-1-one. The reaction was monitored by using gas chromatography

Involvement of chondroitin sulfate E in the liver tumor focal formation of murine osteosarcoma cells

Cell surface heparan sulfate plays a critical role in regulating the metastatic behavior of tumor cells, whereas the role of chondroitin sulfate/dermatan sulfate (CS/DS) has been little understood in this context. Here, we characterized CS/DS chains from the murine osteosarcoma cell line LM8G7, which forms tumor nodules in liver. Structural analysis of the CS/DS chains showed a higher proportion of GlcUAβ1-3GalNAc(4,6-O-disulfate) (E-units) in LM8G7 (12%) than in its parental cell line LM8 (6%), which rarely forms tumors in the liver. Immunostaining with GD3G7, an antibody specific to E-units, confirmed the higher expression of the epitope in LM8G7 than LM8 cells. The tumor focal formation of LM8G7 cells in the liver in mice was effectively inhibited by the pre-administration of CS-E (rich in E-unit) or the pre-incubation of the antibody GD3G7 with the tumor cells. CS-E or GD3G7 inhibited the adhesion of LM8G7 cells to a laminin-coated plate in vitro. In addition, the invasive ability of LM8G7 cells in vitro was also reduced by the addition of CS-E or the antibody. Further, CS-E or the antibody inhibited the proliferation of LM8G7 cells dose-dependently. The binding of LM8G7 cells to VEGF in vitro was also significantly reduced by CS-E and GD3G7. Thus, the present study reveals the significance of highly sulfated CS/DS structures in the liver colonization of osteosarcoma cells and also provides a framework for the development of GAG-based anti-cancer molecules