Daidzein, R-(+)equol and S-(-)equol inhibit the invasion of MDA-MB-231 breast cancer cells potentially via the down-regulation of matrix metalloproteinase-2

PURPOSE: Soy isoflavones may inhibit tumor cell invasion and metastasis via their effects on matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The current study investigates the effects of daidzein, R- and S-equol on the invasion of MDA-MB-231 human breast cancer cells and the effects of these compounds on MMP/TIMP expression at the mRNA level. METHODS: The anti-invasive effects of daidzein, R- and S-equol (0, 2.5, 10, 50 μM) on MDA-MB-231 cells were determined using the Matrigel invasion assay following 48-h exposure. Effects on MMP-2, MMP-9, TIMP-1 and TIMP-2 expression were assessed using real-time PCR. Chiral HPLC analysis was used to determine intracellular concentrations of R- and S-equol. RESULTS: The invasive capacity of MDA-MB-231 cells was significantly reduced (by approximately 50-60 %) following treatment with 50 μM daidzein, R- or S-equol. Anti-invasive effects were also observed with R-equol at 2.5 and 10 μM though overall equipotent effects were induced by all compounds. Inhibition of invasion induced by all three compounds at 50 μM was associated with the down-regulation of MMP-2, while none of the compounds tested significantly affected the expression levels of MMP-9, TIMP-1 or TIMP-2 at this concentration. Following exposure to media containing 50 μM R- or S-equol for 48-h intracellular concentrations of R- and S-equol were 4.38 ± 1.17 and 3.22 ± 0.47 nM, respectively. CONCLUSION: Daidzein, R- and S-equol inhibit the invasion of MDA-MB-231 human breast cancer cells in part via the down-regulation of MMP-2 expression, with equipotent effects observed for the parent isoflavone daidzein and the equol enantiomers.

Tagged phosphine reagents to assist reaction work-up by phase-switched scavenging using a modular flow reactor

The use of three orthogonally tagged phosphine reagents to assist chemical work-up via phase-switch scavenging in conjunction with a modular flow reactor is described. These techniques (acidic, basic and Click chemistry) are used to prepare various amides and tri-substituted guanidines from in situ generated iminophosphoranes.

Surface chemistry of alanine on Cu{111}: Adsorption geometry and temperature dependence

Adsorption of l-alanine on the Cu{111} single crystal surface was investigated as a model system for interactions between small chiral modifier molecules and close-packed metal surfaces. Synchrotron-based X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy are used to determine the chemical state, bond coordination and out-of-plane orientation of the molecule on the surface. Alanine adsorbs in its anionic form at room temperature, whilst at low temperature the overlayer consists of anionic and zwitterionic molecules. NEXAFS spectra exhibit a strong angular dependence of the π ⁎ resonance associated with the carboxylate group, which allows determining the tilt angle of this group with respect to the surface plane (48° ± 2°) at room temperature. Low-energy electron diffraction (LEED) shows a p(2√13x2√13)R13° superstructure with only one domain, which breaks the mirror symmetry of the substrate and, thus, induces global chirality to the surface. Temperature-programmed XPS (TP-XPS) and temperature-programmed desorption (TPD) experiments indicate that the zwitterionic form converts into the anionic species (alaninate) at 293 K. The latter desorbs/decomposes between 435 K and 445 K.

Spontaneous local symmetry breaking: a conformational study of glycine on Cu{311}

Understanding the interplay between intrinsic molecular chirality and chirality of the bonding footprint is crucial in exploiting enantioselectivity at surfaces. As such, achiral glycine and chiral alanine are the most obvious candidates if one is to study this interplay on different surfaces. Here, we have investigated the adsorption of glycine on Cu{311} using reflection-absorption infrared spectroscopy, low-energy electron diffraction, temperature-programmed desorption and first-principles density-functional theory. This combination of techniques has allowed us to accurately identify the molecular conformations present under different conditions, and discuss the overlayer structure in the context of the possible bonding footprints. We have observed coverage-dependent local symmetry breaking, with three-point bonded glycinate moieties forming an achiral arrangement at low coverages, and chirality developing with the presence of two-point bonded moieties at high coverages. Comparison with previous work on the self-assembly of simple amino acids on Cu{311} and the structurally-similar Cu{110} surface has allowed us to rationalise the different conditions necessary for the formation of ordered chiral overlayers.

nor-Mevaldic acid surrogates as selective antifungal agent leads against Botrytis cinerea. Enantioselective preparation of 4-hydroxy-6-(1-phenylethoxy)tetrahydro-2H-pyran-2-one

Solvent-free desymmetrisation of meso-dialdehyde 1 with chiral 1-phenylethan-1-ol, led to preparation of 4-silyloxy-6-alkyloxytetrahydro-2H-pyran-2-one (+)-3a with a 96:4 d.r. Deprotected lactone (+)-19a and the related racemic lactones 16a-18a present a lactone moiety resembling the natural substrate of HMG-CoA reductase and their antifungal properties have been evaluated against the phytopathogenic fungi Botrytis cinerea and Colletotrichum gloeosporioides. These compounds were selectively active against B. cinerea, while inactive against C. gloeosporioides.

Dehydrodipeptide hydrogelators containing naproxen N‑Capped tryptophan: self-assembly, hydrogel characterization, and evaluation as potential drug nanocarriers

In this work, we introduce dipeptides containing tryptophan N-capped with the nonsteroidal anti-inflammatory drug naproxen and C-terminal dehydroamino acids, dehydrophenylalanine (ΔPhe), dehydroaminobutyric acid (ΔAbu), and dehydroalanine (ΔAla) as efficacious protease resistant hydrogelators. Optimized conditions for gel formation are reported. Transmission electron microscopy experiments revealed that the hydrogels consist of networks of micro/nanosized fibers formed by peptide self-assembly. Fluorescence and circular dichroism spectroscopy indicate that the self-assembly process is driven by stacking interactions of the aromatic groups. The naphthalene groups of the naproxen moieties are highly organized in the fibers through chiral stacking. Rheological experiments demonstrated that the most hydrophobic peptide (containing C-terminal ΔPhe) formed more elastic gels at lower critical gelation concentrations. This gel revealed irreversible breakup, while the C-terminal ΔAbu and ΔAla gels, although less elastic, exhibited structural recovery and partial healing of the elastic properties. A potential antitumor thieno[3,2-b]pyridine derivative was incorporated (noncovalently) into the gel formed by the hydrogelator containing C-terminal ΔPhe residue. Fluorescence and Förster resonance energy transfer measurements indicate that the drug is located in a hydrophobic environment, near/associated with the peptide fibers, establishing this type of hydrogel as a good drug-nanocarrier candidate.

Diastereoselective and enantioselective preparation of nor-mevaldic acid surrogates through desymmetrisation methodology. Enantioselective synthesis of (+) and (-) nor-mevalonic lactones

Solvent-free desymmetrisation of a meso-dialdehyde with chiral alcohols, led to preparation of 4-silyloxy-6-alkyloxytetrahydro-2H-pyran-2-one derivatives with a 96% de. This methodology, which yields the corresponding methyl nor-mevaldates with 99% ee, has been applied to the enantioselective synthesis of the (-)-(R) and (+)-(S) nor-mevalonic acid lactones.