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RATIONALE Fucus vesiculosus has been described with potential to develop functional foods containing bioactive compounds against various diseases. However, more studies are needed to better understand its functioning and its previously reported bioactivities, mainly at the molecular level. METHODS An untargeted metabolomic study was performed to analyse HepG2 cells exposed to F. vesiculosus aqueous extract, rich in phlorotannins and peptides, during 24 h. This study was carried out using liquid chromatography combined with high-resolution tandem mass spectrometry. RESULTS This metabolomic study showed significant changes in HepG2 metabolites in the presence of the extract, standing out being the increased intensity of various fatty acid amides (oleamide, (Z)-eicos-11-enamide, linoleamide, palmitamide, dodecanamide and stearamide). This group of metabolites is reported in the literature with anticancer and hypocholesterolemic activity, bioactivities also described for F. vesiculosus. The extract induced, likewise, the expression of glutathione indicating its antioxidant effect. CONCLUSIONS This study demonstrated the potential of the compounds present in the F. vesiculosus aqueous extract for the development of natural drugs, nutraceuticals or dietary supplements, justified at the molecular level by changes in cell metabolites related to anticancer and hypocholesterolemic activity. The results here described, using an untargeted metabolomic approach, may contribute to a better understanding of algal behaviour, when used as food, in health-promoting effects.

Chronic obstructive pulmonary disease (COPD) is a major increasing health problem and the World Health Organization (WHO) reports COPD as the fifth leading cause of death worldwide. COPD refers to a condition of inflammation and progressive weakening of the structure of the lung as well as irreversible narrowing of the airways. Current treatment is only palliative and no available drug halts the progression of the disease. Human neutrophil elastase (HNE) is a serine protease, which plays a major role in the COPD inflammatory process. The protease/anti-protease imbalance leads to an excess of extracellular HNE hydrolyzing elastin, the structural protein that confers elasticity to the lung tissue. Although HNE was identified as a therapeutic target for COPD more than 30 years ago, only Sivelestat (ONO-5046), an HNE inhibitor from Ono Pharmaceutical, has been approved for clinical use. Nevertheless, Sivelestat is only approved in Japan and its development in the USA was terminated in 2003. Other inhibitors in pre-clinical or phase I trials were discontinued for various reasons. Hence, there is an urgent need for low-molecular-weight synthetic elastase inhibitors and the present review discusses the recent advances on this field covering acylating agents, transition-state inhibitors, mechanism-based inhibitors, relevant natural products, and major patent disclosures.

Phototoxic and radical-generating debromination reactions of monobrominated hypericin with bromine at one of four possible positions were investigated using density functional theory. The study was performed on two closely lying conformational isomers, differing in the relative orientations of the two anthracene units of the hypericin core. Calculated adiabatic electron affinities show that the molecules have the ability to, in aqueous solution, extract an electron from the surrounding. The electron might then be passed on to molecular oxygen, forming reactive superoxide radical anions. If electron extraction from the molecule does not occur in this step, the molecule might dissociate, generating a negatively charged bromine as a leaving group and a hypericin radical capable of forming direct binding to biological molecules. This reaction was found possible for those species substituted by Br at two of the four positions, with barriers of similar to 13 kcal/mol in aqueous solution. Debromination was not found energetically possible for neither the neutral ground state compounds nor the bay-deprotonated species. (c) 2008 Wiley Periodicals, Inc.

We are reporting ab initio and density functional theory (DFT) calculations for the phenol O–H bond dissociation energy in the gas phase and in phenol–water clusters. We have tested a series of recently proposed functionals and verified that DFT systematically underestimates the O–H bond dissociation energy of phenol. However, O–H bond dissociation energies in water clusters are in reasonable agreement with experimental data for phenol in solution. We have evaluated electronic difference densities in phenol–water, phenoxy–water, and water, and we are suggesting that the representation of this quantity gives an interesting picture of the electronic density rearrangement induced by hydrogen bond interactions in phenol–water clusters. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001

The standard molar enthalpies of formation of chloro-, bromo-, and iodoacetic acids in the crystalline state, at 298.15 K, were determined as ΔfH(C2H3O2Cl, cr α)=−(509.74±0.49) kJ mol−1, ΔfH(C2H3O2Br, cr I)=−(466.98±1.08) kJ mol−1, and ΔfH (C2H3O2I, cr)=−(415.44±1.53) kJ mol−1, respectively, by rotating-bomb combustion calorimetry. Vapor pressure versus temperature measurements by the Knudsen effusion method led to ΔsubH(C2H3O2Cl)=(82.19±0.92) kJ mol−1, ΔsubH(C2H3O2Br)=(83.50±2.95) kJ mol−1, and ΔsubH(C2H3O2I)=(86.47±1.02) kJ mol−1, at 298.15 K. From the obtained ΔfH(cr) and ΔsubH values it was possible to derive ΔfH(C2H3O2Cl, g)=−(427.55±1.04) kJ mol−1, ΔfH(C2H3O2Br, g)=−(383.48±3.14) kJ mol−1, and ΔfH(C2H3O2I, g)=−(328.97±1.84) kJ mol−1. These data, taken with a published value of the enthalpy of formation of acetic acid, and the enthalpy of formation of the carboxymethyl radical, ΔfH(CH2COOH, g)=−(238±2) kJ mol−1, obtained from density functional theory calculations, led to DH(H−CH2COOH)=(412.8±3.2) kJ mol−1, DH(Cl−CH2COOH)=(310.9±2.2) kJ mol−1, DH(Br−CH2COOH)=(257.4±3.7) kJ mol−1, and DH(I−CH2COOH)=(197.8±2.7) kJ mol−1. A discussion of the C−X bonding energetics in XCH2COOH, CH3X, C2H5X, C2H3X, and C6H5X (X=H, Cl, Br, I) compounds is presented.

Herein we demonstrate for the first time that a boron promoted one-pot assembly reaction may be used to discover novel enzyme inhibitors. Inhibitors for HNE were simply assembled in excellent yields, high diastereoselectivities and IC50 up to 1.10 μM, based on components like salicylaldehyde, aryl boronic acids and amino acids. The combination of synthetic, biochemical, analytical and theoretical studies allowed the identification of the 4-methoxy or the 4-diethyl amino substituent of the salicylaldehyde as the most important recognition moiety and the imine alkylation, lactone ring opening as key events in the mechanism of inhibition.