Juan Galisteo

Endogenous and dietary indoles: a class of antioxidants and radical scavengers in the ABTS assay.

Indoles are very common in the body and diet and participate in many biochemical processes. A total of twenty-nine indoles and analogs were examined for their properties as antioxidants and radical scavengers against 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) ABTS•+ radical cation. With only a few exceptions, indoles reacted nonspecifically and quenched this radical at physiological pH affording ABTS. Indoleamines like tryptamine, serotonin and methoxytryptamine, neurohormones (melatonin), phytohormones (indoleacetic acid and indolepropionic acid), indoleamino acids like l-tryptophan and derivatives (N-acetyltryptophan, l-abrine, tryptophan ethyl ester), indolealcohols (tryptophol and indole-3-carbinol), short peptides containing tryptophan, and tetrahydro-β-carboline (pyridoindole) alkaloids like the pineal gland compound pinoline, acted as radical scavengers and antioxidants in an ABTS assay-measuring total antioxidant activity. Their trolox equivalent antioxidant capacity (TEAC) values ranged from 0.66 to 3.9 mM, usually higher than that for Trolox and ascorbic acid (1 mM). The highest antioxidant values were determined for melatonin, 5-hydroxytryptophan, trp-trp and 5-methoxytryptamine. Active indole compounds were consumed during the reaction with ABTS•+ and some tetrahydropyrido indoles (e.g. harmaline and 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid ethyl ester) afforded the corresponding fully aromatic β-carbolines (pyridoindoles), that did not scavenge ABTS•+. Radical scavenger activity of indoles against ABTS•+ was higher at physiological pH than at low pH. These results point out to structural compounds with an indole moiety as a class of radical scavengers and antioxidants. This activity could be of biological significance given the physiological concentrations and body distribution of some indoles.

Self-assembly approach to optical metamaterials

Photonic crystals can be viewed just as a subclass of a larger family of material systems called metamaterials in which the properties largely derive from the structure rather than from the material itself. Opals have only a relatively recent history as photonic bandgap materials and have received a strong thrust from their adequacy as scaffoldings for further templating other materials with photonic applications for instance. The tortuous route from materials to devices might perhaps find reward in the ease and low cost of fabrication of these materials. In this paper we present a review of recent work and work under way in our laboratory tending towards synthesis based on self-assembly to realize metamaterials in the optical range. This comprises the formation of the templates (opals) and subsequent synthesis of guest materials such as semiconductors, metals and insulators. The possibility of further processing allows additional two-dimensional and quasi-two-dimensional patterning for the design of new structures. In this paper we show how the raw matter can be checked for quality and learn how to use its optical properties to evaluate application potential. Issues relating to the optical properties (such as crystalline quality, finite size effects and infiltration with other materials) are examined. We show some examples where opals are used to pattern the growth of other materials with photonic applications (such as metals and semiconductors) and developments leading to both vertical and lateral engineering are shown.

Simultaneous generation of second to fifth harmonic conical beams in a two dimensional nonlinear photonic crystal.

Broadly tunable multiple high-harmonic conical beams have been generated by means of a multistep χ(2) cascade processes in a two dimensional nonlinear photonic crystal. The nonlinear structure consists of a square lattice of inverted hexagonal domains with diameters and distances between domains as low as 1 μm. The large number of reciprocal lattice vectors provided by both the square nonlinear structure and the hexagonal shaped domains, along with imperfections on the size and shape of the individual domains make possible the simultaneous generation of second up to fifth harmonic conical beams in a single nonlinear structure by using different types of phase matching geometries. The frequency response can be tuned in an extremely large spectral range, and continuous generation of nonlinear conical beams covering the whole visible spectral region can be achieved. Further, the same photon energy can be generated at different orders, so that concentrically emitted conical beams with angular dispersion as large as Δθ = 50° can be observed. The results highlight the significance of highly controlled engineered 2D nonlinear structures to generate advanced multi-photon devices with large spatial and spectral tunable response.

Naturally-occurring tetrahydro-β-carboline alkaloids derived from tryptophan are oxidized to bioactive β-carboline alkaloids by heme peroxidases.

β-Carbolines are indole alkaloids that occur in plants, foods, and endogenously in mammals and humans, and which exhibit potent biological, psychopharmacological and toxicological activities. They form from naturally-occurring tetrahydro-β-carboline alkaloids arising from tryptophan by still unknown way and mechanism. Results in this research show that heme peroxidases catalyzed the oxidation of tetrahydro-β-carbolines (i.e. 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid and 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid) into aromatic β-carbolines (i.e. norharman and harman, respectively). This oxidation followed a typical catalytic cycle of peroxidases through redox intermediates I, II, and ferric enzyme. Both, plant peroxidases (horseradish peroxidase, HRP) and mammalian peroxidases (myeloperoxidase, MPO and lactoperoxidase, LPO) catalyzed the oxidation in an efficient manner as determined by kinetic parameters (VMAX and KM). Oxidation of tetrahydro-β-carbolines was inhibited by peroxidase inhibitors such as sodium azide, ascorbic acid, hydroxylamine and excess of H2O2. The formation of aromatic β-carbolines by heme peroxidases can help to explain the presence and activity of these compounds in biological systems.

Metabolite profile resulting from the activation/inactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 2-methyltetrahydro-β-carboline by oxidative enzymes.

Metabolic enzymes are involved in the activation/deactivation of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyiridine (MPTP) neurotoxin and its naturally occurring analogs 2-methyltetrahydro-β-carbolines. The metabolic profile and biotransformation of these protoxins by three enzymes, monoamine oxidase (MAO), cytochrome P450, and heme peroxidases (myeloperoxidase and lactoperoxidase), were investigated and compared. The metabolite profile differed among the enzymes investigated. MAO and heme peroxidases activated these substances to toxic pyridinium and β-carbolinium species. MAO catalyzed the oxidation of MPTP to 1-methyl-4-phenyl-2,3-dihydropyridinium cation (MPDP+), whereas heme peroxidases catalyzed the oxidation of MPDP+ to 1-methyl-4-phenylpyridinium (MPP+) and of 2-methyltetrahydro-β-carboline to 2-methyl-3,4-dihydro-β-carbolinium cation (2-Me-3,4-DHβC+). These substances were inactivated by cytochrome P450 2D6 through N-demethylation and aromatic hydroxylation (MPTP) and aromatic hydroxylation (2-methyltetrahydro-β-carboline). In conclusion, the toxicological effects of these protoxins might result from a balance between the rate of their activation to toxic products (i.e., N-methylpyridinium-MPP+ and MPDP+- and N-methyl-β-carbolinium—βC+—) by MAO and heme peroxidases and the rate of inactivation (i.e., N-demethylation, aromatic hydroxylation) by cytochrome P450 2D6.

Synthesis and cytotoxic activity of a new potential DNA bisintercalator: 1,4-Bis{3-[N-(4-chlorobenzo[g]phthalazin-1-yl)aminopropyl]}piperazine

The synthesis of new 1,4-bisalkylamino (2-4) and 1-alkylamino-4-chloro (5-6) substituted benzo[g]phthalazines is reported. Compounds 2-4 and 6 were prepared both in the free and heteroaromatic ring protonated forms. Bifunctional 6 contains the 1,4-bisaminopropylpiperazine chain as a linker between the two heteroaromatic units, whereas 5 is its monofunctional analogue. The in vitro antitumour activity of the synthesized compounds has been tested against human colon, breast and lung carcinoma cells, and also against human glioblastoma cells. Results obtained show that all of them are active in all cases, but bifunctional 6.2HCl is remarkably effective against the four cell lines tested, exhibiting IC50 values in the range of 10(-7) M, similar to those found for doxorubicin. The bifunctional structure of 6.2HCl enhances activity with respect to the monofunctional related compounds 5 and 7, leading to the highest activity among all the compounds tested. Molecular modelling of 6 suggests that those results could be indicative of DNA bisintercalation, which should be specially favoured in the diprotonated form 6.2HCl, a compound suitable for being studied more in depth in further biological tests. Measure of the DNA thermal melting curves show that the linear rise in Tm for bifunctional 6.2HCl is nearly twice than that one obtained for monofunctional 5, and supports the DNA-binding hypothesis.