Publications

Abstract The crystal structures of three benzamide derivatives, viz. N-(6-hydroxyhexyl)-3,4,5-trimethoxybenzamide, C16H25NO5, (1), N-(6-anilinohexyl)-3,4,5-trimethoxybenzamide, C22H30N2O4, (2), and N-(6,6-diethoxyhexyl)-3,4,5-trimethoxybenzamide, C20H33NO6, (3), are described. These compounds differ only in the substituent at the end of the hexyl chain and the nature of these substituents determines the differences in hydrogen bonding between the molecules. In each molecule, the m-methoxy substituents are virtually coplanar with the benzyl ring, while the p-methoxy substituent is almost perpendicular. The carbonyl O atom of the amide rotamer is trans related with the amidic H atom. In each structure, the benzamide N-H donor group and O acceptor atoms link the molecules into C(4) chains. In 1, a terminal -OH group links the molecules into a C(3) chain and the combined effect of the C(4) and C(3) chains is a ribbon made up of screw related R-2(2) (17) rings in which the center dot center dot center dot O-H center dot center dot center dot chain lies in the centre of the ribbon and the trimethoxybenzyl groups forms the edges. In 2, the combination of the benzamide C(4) chain and the hydrogen bond formed by the terminal N-H group to an O atom of the 4-methoxy group link the molecules into a chain of R-2(2) (17) rings. In 3, the molecules are linked only by C(4) chains.

Abstract Three coumarin derivatives, viz. 6-methyl-N-(3-methylphenyl)-2-oxo-2H-chromene-3-carboxamide, C18H15NO3 (1), N-(3-methoxyphenyl)-6-methyl-2-oxo-2H-chromene-3-carboxamide, C18H15NO4 (2), and 6-methoxy-N-(3-methoxyphenyl)-2-oxo-2H-chromene-3-carboxamide, C18H15NO5 (3), were synthesized and structurally characterized. The molecules display intramolecular N-H center dot center dot center dot O and weak C-H center dot center dot center dot O hydrogen bonds, which probably contribute to the approximate planarity of the molecules. The supramolecular structures feature C-H center dot center dot center dot O hydrogen bonds and pi-pi interactions, as confirmed by Hirshfeld surface analyses.

Abstract Due to the generalization of electronically supported activities, we anticipate that, in the near future, the letter "e" in "e-learning," indicating the use of electronic media and information and communication technologies in education, will be dropped and that "e-learning" will be referred to as simply "learning." This paper presents an attempt at understanding the causes of the name shift and at predicting its consequences. We offer a constructive reflection on how e-learning has been looked upon and on what we foresee will happen in the future, drawing briefly on several areas of knowledge and on the experience of the authors as educators at university, teacher training and high school levels. Our effort has also resulted in greater awareness of the importance of social tools and of the relevance of the human factor in the learning process.

Abstract The majority of current infectious diseases are almost untreatable by conventional antibiotic therapy given the advent of multidrug-resistant bacteria. The degree of severity and the persistence of infections are worsened when microorganisms form biofilms. Therefore, efforts are being applied to develop new drugs not as vulnerable as the current ones to bacterial resistance mechanisms, and also able to target bacteria in biofilms. Natural products, especially those obtained from plants, have proven to be outstanding compounds with unique properties, making them perfect candidates for these much-needed therapeutics. This review presents the current knowledge on the potentialities of plant products as antibiotic adjuvants to restore the therapeutic activity of drugs. Further, the difficulties associated with the use of the existing antibiotics in the treatment of biofilm-related infections are described. To counteract the biofilm resistance problems, innovative strategies are suggested based on literature data. Among the proposed strategies, the use of phytochemicals to inhibit or eradicate biofilms is highlighted. An overview on the use of phytochemicals to interfere with bacterial quorum sensing (QS) signaling pathways and underlying phenotypes is provided. The use of phytochemicals as chelating agents and efflux pump inhibitors is also reviewed.

Abstract Background: The systemic information enclosed in microarray data encodes relevant clues to overcome the poorly understood combination of genetic and environmental factors in Parkinson's disease (PD), which represents the major obstacle to understand its pathogenesis and to develop disease-modifying therapeutics. While several gene prioritization approaches have been proposed, none dominate over the rest. Instead, hybrid approaches seem to outperform individual approaches. Methods: A consensus strategy is proposed for PD related gene prioritization from mRNA microarray data based on the combination of three independent prioritization approaches: Limma, machine learning, and weighted gene co-expression networks. Results: The consensus strategy outperformed the individual approaches in terms of statistical significance, overall enrichment and early recognition ability. In addition to a significant biological relevance, the set of 50 genes prioritized exhibited an excellent early recognition ability (6 of the top 10 genes are directly associated with PD). 40 % of the prioritized genes were previously associated with PD including well-known PD related genes such as SLC18A2, TH or DRD2. Eight genes (CCNH, DLK1, PCDH8, SLIT1, DLD, PBX1, INSM1, and BMI1) were found to be significantly associated to biological process affected in PD, representing potentially novel PD biomarkers or therapeutic targets. Additionally, several metrics of standard use in chemoinformatics are proposed to evaluate the early recognition ability of gene prioritization tools. Conclusions: The proposed consensus strategy represents an efficient and biologically relevant approach for gene prioritization tasks providing a valuable decision-making tool for the study of PD pathogenesis and the development of disease-modifying PD therapeutics.

Abstract Adenosine receptors (AR) are GPCRs involved in several biochemical processes. Agents able to selectively modulate the activity of these receptors represent promising multifunctional agents to delay or slow the progression of a large range of diseases. Here, differently substituted 3-thiophenylcoumarins are described that exert affinity towards human AR subtypes. Among the compounds synthesized, the 3-(4-bromothiophenyl) derivative 11 showed the highest affinity and selectivity for the hA(3) AR (K-i = 740 nM). Interestingly, the current study revealed that small structural changes in this scaffold allow modulating the AR affinity, suggesting that this scaffold has desirable properties for the development of promising classes of hA(1), hA(2A), and/or hA(3) AR ligands. Further docking calculations in the hA(3) AR identified the hypothetical binding mode of the most active and selective compounds. In addition, theoretical evaluation of some physicochemical properties highlighted the potential of these compounds as drug candidates. The data so far acquired is the first step for further optimization of these 3-thiophenylcoumarins as hA(3) AR selective ligands.

Abstract The indiscriminate use of biocides for general disinfection has contributed to the increased incidence of antimicrobial tolerant microorganisms. This study aims to assess the potential of seven phytochemicals (tyrosol, caffeic acid, ferulic acid, cinnamaldehyde, coumaric acid, cinnamic acid and eugenol) in the control of planktonic and sessile cells of Staphylococcus aureus and Escherichia coli. Cinnamaldehyde and eugenol showed antimicrobial properties, minimum inhibitory concentrations of 3-5 and 5-12 mM and minimum bactericidal concentrations of 10-12 and 10-14 mM against S. aureus and E. coli, respectively. Cinnamic acid was able to completely control adhered bacteria with effects comparable to peracetic acid and sodium hypochlorite and it was more effective than hydrogen peroxide (all at 10 mM). This phytochemical caused significant changes in bacterial membrane hydrophilicity. The observed effectiveness of phytochemicals makes them interesting alternatives and/or complementary products to commonly used biocidal products. Cinnamic acid is of particular interest for the control of sessile cells.

Abstract This paper reports an experimental and theoretical study on the structural and energetic characterization of the 2-mercaptoimidazole (2-MI) in the solid and in the gaseous phases. The single crystal X-ray diffraction determinations on the anhydrous and hemihydrate 2-MI forms were carried out at T = (296 +/- 2) K and T = (150 +/- 2) K, respectively, and suggest that in both forms the 2-MI molecule is closer to the thione conformation, albeit some single bond character is possible. The energy of combustion of the title compound was measured by rotating-bomb combustion calorimetry, being used to derive the corresponding enthalpy of formation in the crystalline-phase. The enthalpy of sublimation of 2-MI, at T = 298.15 K, was obtained from high temperature Calvet microcalorimetry measurements. These two parameters yielded the gas-phase enthalpy of formation, allowing the inherent energetic analysis of the molecule. This result was discussed together with the corresponding predictions for 2-MI and its tautomer, 1,3-dihydro-2H-imidazole-2-thione, by the G3 method. The dehydration reaction of 2-MI center dot 0.5H(2)O(cr) was also investigated and the corresponding enthalpy of dehydration was determined by Calvet microcalorimetry.

Abstract The number of people affected by neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease is rapidly increasing owing to the global increase in life expectancy. Small molecules with neurotrophic effects have great potential for management of these neurological disorders. In this study, different (C1-C12) alkyl ester derivatives of hydroxycinnamic acids (HCAs) were synthesized (a total of 30 compounds). The neurotrophic capacity of the test compounds was examined by measuring promotion of survival in serum-deprived conditions and enhancement of nerve growth factor (NGF)-induced neurite outgrowth in PC12 neuronal cells. p-Coumaric, ferulic, and sinapic acids and their esters did not alter cell survival, while caffeic acid and all its alkyl esters, especially decyl and dodecyl caffeate, significantly promoted neuronal survival at 25m. Methyl, ethyl, propyl, and butyl caffeate esters also significantly enhanced NGF-induced neurite outgrowth, among which the most effective ones were propyl and butyl esters, which at 5m led to 25- and 22-fold increases in the number of neurites, respectively. The findings of the docking study suggested phosphatidylinositol 3-kinase (PI3K) as the potential molecular target. In conclusion, our findings demonstrate that alkyl esters of caffeic acid can be useful as scaffolds for the discovery of therapeutic agents for neurodegenerative diseases.

Abstract Detection and quantification of cocaine is a key tool in fields such as police apprehensions and the fight against drug trafficking. Thus, a simple, fast and inexpensive electroanalytical methodology for the determination of cocaine in seized street samples has been developed, employing linear sweep voltammetry. The method is based on the use of a glassy carbon (GC) electrode modified by a combination of multi-walled carbon nanotubes (MWCNT) with beta-cyclodextrin (beta-CD) incorporated in a polyaniline film. The proposed method shows high reproducibility, repeatability and specificity. Under optimal conditions, the beta-CD/MWCNT-modified GC electrode gives a detection limit of 1.02 mu M cocaine. The results obtained are in good agreement with those obtained by the high-performance liquid chromatography reference method. The new methodology proposed has excellent potential as the basis of a portable analytical sensor for on-site screening of cocaine in seized street samples.