Publications

Abstract The chain-length dependence of the thermodynamic properties associated with the solid-to-liquid, liquid-to-gas, and solid-to-gas phase equilibria is analyzed and discussed for homologous families of linear alpha,omega-disubstituted alkanes, R-(CH2)(n)-R series. A remarkable alternation on the melting properties exhibited by even and odd-numbered alkanes is clearly emphasized in their a,w-disubstituted derivatives since the even members display increased properties due to their higher crystal packing density. The odd-even effect is also perceived in the values of Delta H-sub degrees and Delta S-sub degrees. Strong hydrogen bonding contributes to high boiling points and Delta H-vap degrees values evidenced by alkane-alpha,omega-diols. Moreover, the anomalously low values of Delta H-sub degrees and Delta H-vap degrees reported for larger dicarboxylic acids suggest the formation, in the vapor phase, of hydrogen-bonded cyclic structures. Furthermore, the analysis of the Delta H-fus degrees/Delta H-sub degrees and Delta S-sub degrees/Delta S-sub degrees ratios is used to highlight the contribution of functional groups to the cohesive interaction preserved in the liquid phase after a fusion transition. The thermodynamic interpretation indicates a higher structuration in the liquid alkane-alpha,omega-diols and alkane-alpha,omega-dioic acids, which have lower ratios of Delta H-fus degrees/A(sub)H degrees than corresponding n-alkanes. In addition, the thermodynamic analysis supports that hydrogen bonding in the liquid phase of alkanamines or alkane-alpha,omega-diamines has a significant low contribution to the overall intermolecular interactions.

Abstract Currently, peripheral COMT inhibitors have an important role in the treatment of Parkinson's disease, and central COMT inhibitors have a potential role in the treatment of various neuropsychiatric disorders, such as attention deficit hyperactivity disorder. Adverse reactions, low bioavailability and short elimination half-lives have prompted the development of new selective COMT inhibitors. The objective of this study was to evaluate the pharmacodynamic properties of novel tight-binding COMT inhibitors (NC, NE, NDE, NCAPE, CNCAFBn, CNCAPE, NCAFBn, CNCAPA, CNCABA and CNCAHA) and compared to standard inhibitors tolcapone and entacapone. The activity of soluble (S) and membrane bound (MB) COMT from rat liver and brain was assessed in the presence of varying concentrations of each inhibitor. NE and NC behaved most potently against liver S-COMT, and CNCAPE was the most potent inhibitor against brain MB-COMT. The cytotoxicity of tolcapone and CNCAPE in human neuroblastoma SK-N-SH cells and human liver adenocarcinoma SK-HEP-1 cells was also assessed. At lower concentrations, CNCAPE did not reduce cell viability, suggesting that CNCAPE may have a potential therapeutic role as a centrally active COMT inhibitor.

Abstract Drug repurposing arises as an interesting alternative to overcome the limited efficacy of current available antibiotics by reducing time, cost and risk associated with drug innovation. In this study, the activity of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), was evaluated on the control of preestablished adhered cells (2 h) and 24 h old biofilms of Staphylococcus aureus. Bacterial adhesion was performed by S. aureus CECT 976, while biofilm formation was also performed by the antibiotic-resistant strains: SA1199B, RN4220 and XU212. The treatment with ibuprofen promoted metabolic reductions up to 80% and total loss of culturability of adhered cells and 24 h old biofilms. Ibuprofen demonstrated moderate efficacy to remove biofilms of S. aureus CECT 976 (removal <= 40%), but did not display removal action against the antibiotic-resistant strains. Antibacterial activity (inhibitory and bactericidal) and mode of action of ibuprofen were also assessed using different bacterial physiological indices. Minimum inhibitory and bactericidal concentrations of the four S. aureus strains ranged between 500 and 2000 mg L-1 and 1400 - >2000 mg L-1, respectively. After S. aureus CECT 976 incubation with ibuprofen, cell permeation to propidium iodide, release of intracellular potassium and changes on cell surface hydrophobicity were observed. The overall results, demonstrate that ibuprofen can control S. aureus planktonic and sessile growth, with strong destabilizing and disrupting action on the cytoplasmic membrane.

Abstract The purpose of this study was to examine the neuroprotective effects of caffeic acid hexyl (CAF6) and dodecyl (CAF12) amide derivatives on the early stage of retinopathy in streptozotocin-induced diabetic rats. Animals were divided in five groups (n=8/group); one group consisted of non-diabetic rats as control, while the other four were diabetic animals either non-treated or treated with CAF6, CAF12 or resveratrol intravitreally for four weeks. Retinal superoxide dismutase (SOD) activity and 8-iso-prostaglandin F-2 alpha (iPF(2 alpha)) levels were evaluated by an ELISA assay. Phosphorylation of ERK1/2 and AKT was determined by immunoblotting in retinal homogenates. Retinal morphology was also examined using light microscopy. Treatment with CAF6 and CAF12 increased retinal SOD activity, while it decreased iPF(2 alpha) levels in diabetic rats. Phosphorylation of ERK1/2 was increased, while AKT phosphorylation was decreased in diabetic rats compared to normal control and these alterations were significantly reversed in diabetic rats treated with CAF6 and CAF12. Furthermore, thickness of the whole retinal layer, outer nuclear layer, and ganglion cell count were decreased in diabetic rats compared to control and CAF6 and CAF12 treatments prevented these changes. CAF6 and CAF12 seem to be effective agents for treatment of diabetic retinopathy via attenuation of retinal oxidative stress and improvement of neuronal survival signaling.

Abstract The conspicuous absence of novel and effective strategies to control microbial growth, both in the food and healthcare industries and evidence of increasing microbial resistance to conventional biocides has led to a search for novel antimicrobials and growth prevention strategies. In this study, 15 phytochemicals and derivatives, structurally-related to cinnamic acid and cinnamaldehyde, were assessed for their effects on the growth of Escherichia colt, Staphylococcus aureus and Enterococcus hirae. Their effects were compared to seven commonly used biocides (hydrogen peroxide, sodium hypochlorite, chlorhexidine, cetyltrimethylammonium bromide, triclosan, o-phthalaldehyde and lactic acid). All phytochemicals and derivatives increased lag phase and culture doubling time of the tested bacteria. Cinnamic acid and other derivatives inhibited bacterial growth. The MIC of cinnamaldehyde was comparable to o-phthalaldehyde and sodium hypochlorite and lower than hydrogen peroxide and lactic acid. The effect of methyl trans-cinnamate on bacterial growth was more evident against Gram-negative bacteria. It also inhibited quorum sensing in Chromobacterium violaceum. The effect of phytochemicals against sessile bacteria was low: < 1 log CFU.cm(-2). Inhibition of quorum sensing and of bacterial growth supports the fact that phytochemicals are an interesting source of antimicrobials with potential use as biocides or more likely as additives to improve the efficacy of current biocidal formulations and preservative systems.

Abstract Reduced glutathione (GSH)is the most abundant low molecular weight thiol-containing tripeptide (glycine, cysteine, and glutamate) which is synthesized in the cells. GSHplays critical roles in protecting cells from oxidative damage and the toxicity of xenobiotics. Besides, it is also involved in the regulation of intracellular redox homeostasis, which leads to its oxidation into oxidized glutathione (GSSG). Determining the ratio of GSH/GSSG in different biological samples is a major procedure for the evaluation of an individual’s oxidative status and can be a potential biomarker of oxidative stress.

Abstract This paper, reports for the first time the green synthesis of the polymorphs I and II of new pharmaceutical co-crystals lamivudine:theophylline in solid-phase, through the mixture between lamivudine and theophylline (both active pharmaceutical ingredients-APIs) in the proportion of 1:1 by neat grinding and liquid assisted grinding (10 mu L ethanol). Fourier transform-infrared (FT-IR) spectroscopy and multivariate curve resolution with alternating least-squares (MCR-ALS) were employed as non-invasive analytical methodology for the at-line green synthesis monitoring of the novels lamivudine:theophylline co-crystals. By MCR-ALS it was possible to identify each component present in a complex matrix, with strong spectral overlapping, containing lamivudine, theophylline, and the novel lamivudine:theophylline co-crystal with high confidence based on the comparison of the pure and recovered spectral and concentration profiles. This model allowed to identify the end of the reaction and understand the mechanism involved in the synthesis through the identification of the intermediates present in the synthesis process. Also, MCR-ALS model estimated the concentration of co-crystal polymorph I with a root mean square error of prediction (RMSEP) and the percentage relative error of prediction (REP%) equal to 3.323 (w/w) and 9.9%, respectively. These were good results since the spectral profile of cocrystal and the physical mixture of its APIs present strong spectral overlapping in their spectral domain. Therefore, the quantification of the co-crystal between its APIs (lamivudine and theophylline) certified that the co-crystal as final product was obtained, collaborating with the results obtained by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD).

Abstract Here we report the near-infrared-upconversion (NIR-UC) luminescence of the organic dye fluorescein, without the need of metal-based NIR-UC materials or the use of high-energy and high-cost two-photon absorption excitation (TPA) systems. Fluorescein upconverts NIR light (lambda = 920 nm) to visible light (lambda = 545 nm) in aqueous solutions, with a pH-dependent light-intensity, by using a low-energy and low-cost nanosecond pulsed laser. The NIR-UC of fluorescein is explained with a triplet-triplet annihilation (TTA) mechanism, assisted by molecular vibrations. This work opens the door for deep-penetration bioimaging and photodynamic therapy, as well for NIR-excited TTA, photocatalysis and photovoltaics, by using solely high quantum yield organic molecules.

Abstract Chemical functionalization of multiwalled carbon nanotubes (MWCNTs) is important from the view point of polymer based composite manufacturing. As pristine MWCNTs has certain disadvantage such as they have lower dispersion, they are hydrophobic and are not readily soluble in a solvent, these characteristics makes them unreliable candidate for most of the industrial applications. By doing chemical functionalization of MWCNTs, these shortcomings can be overcome, and the MWCNTs can be used as a filler in composite manufacturing. This has the advantage of better nanofillers’ dispersion and provide the better interfacial bonding. In this study, MWCNTs are functionalized by the carboxylic group, chemical functionalization of MWCNTs is an optimization problem, governed by parameters like mixture acid concentration, temperature, time of heating and amount of MWCNTs used. Material characterization of MWCNTs is done and test specimens are manufactured according to different concentrations of MWCNTs within a bio-based epoxy resin. Mechanical properties are then compared according to different concentrations. These mechanical and material characterizations increase the understanding of chemical functionalization by carboxylic group and the influence of the concentration of MWCNTs dispersed within the bio-based resin matrix.