Publications

Abstract Waterborne diseases continue to be an important cause of illness and death with particular incidence in developing countries. Indeed, the use of contaminated drinking water (DW) has been linked with several health problems worldwide. So, the main goal of water companies is to ensure that water is microbiologically and chemically safe for consumers. Many of the problems in DW distribution systems (DWDS) are microbiological and thus the prevention of water associated problems has mainly focused on these contaminations. There are several public health relevant microorganisms that may be transmitted through contaminated DW and infect humans. Even more worrying is the fact that waterborne bacterial pathogens have the potential to become components of sessile microbial communities. Biofilms can act as environmental reservoirs of coliforms (intestinal and non-intestinal origin) and other clinically relevant pathogens, representing a potential source of water contamination. The presence of biofilms in DWDS constitutes special concern because they provide the ideal environment for pathogens to survive and persist for long time in distribution networks. As biofilms are recalcitrant to treatment, they also contribute to the reduced efficiency of disinfection programs. This chapter provides an overview about the involvement of biofilms in waterborne diseases. In addition, the impact of the presence of biofilms in DWDS and on the organoleptic quality of the distributed water will be also discussed. As Escherichia coli is an indicator of fecal contamination and some of their variants, enterotoxigenic and enterohemorrhagic, are one of the major causes of water-related outbreaks, their role will be also highlighted.

Abstract Antimicrobial resistance is one of the most serious public health problems. This is of particular concern when bacteria become resistant to various antimicrobial agents simultaneously and when they form biofilms. Consequently, therapeutic options for the treatment of infections have become limited, leading frequently to recurrent infections, treatment failure and increase of morbidity and mortality. Both, persistence and spread of antibiotic resistance, in combination with decreased effectiveness and increased toxicity of current antibiotics have emphasized the urgent need to search alternative sources of antimicrobial substances. Plants are recognized as a source of unexplored chemical structures with high therapeutic potential, including antimicrobial activity against clinically important microorganisms. Additionally, phytochemicals (plant secondary metabolites) present several advantages over synthetic molecules, including green status and different mechanisms of action from antibiotics which could help to overcome the resistance problem. In this study, an overview of the main classes of phytochemicals with antimicrobial properties and their mode of action is presented. A revision about the application of phytochemicals for biofilm prevention and control is also done. Moreover, the use of phytochemicals as scaffolds of new functional molecules to expand the antibiotics pipeline is reviewed.

Abstract In this contribution, we attempted to design novel inhibitors of the serine/threonine-protein kinase Chk1. After studying the interaction of Chk1 ATP binding site with known inhibitor C39, we created seven modified C39-based molecules in order to achieve higher binding potentials. Of those, modified molecules 2, 4, 6 and 7 (MD2, MD4, MD6 and MD7) were selected to be assembled in three new molecules, originating MD8, MD9 and MD10. When compared to C39, MD8 and MD9 showed significant improvements in the binding energy while MD10 had a smaller gain. MD9 achieved the best improvement (21%) and MD8 the second best (19%) while MD10 only reached a 6% improvement.

Abstract Zinc oxide is widely used in the manufacture of a vast number of consumer goods and industrial applications. The employ of nano and sub-micrometer zinc oxide materials has recently been introduced as a more economic and more effective alternative to bulk zinc oxide. Furthermore zinc oxide is being used as antibacterial material since metal oxides are recognized as possessing antibacterial properties and are regarded as safe materials to human beings and animals. The present work aims to present our study on the antibacterial properties of zinc oxide particles prepared by a polyol thermal method. Spherical submicrometer ZnO particles were prepared and their antibacterial properties were tested in aqueous suspensions of E. coli bacteria. For ZnO concentrations higher than 50 ppm an inhibition of the growth rate of bacteria higher than 95 % is achieved.

Abstract An amperometric ion sensor featuring a microhole supported water/organic gel interface was developed for the quantitative analysis of a water-soluble anticancer drug species, namely, topotecan, which has been used for ovarian and lung cancer treatments. Voltammetric responses associated with topotecan transfer across a polarized water/1,2-dichloroethane (1,2-DCE) interface were first investigated at different aqueous pH values to provide information on a topotecan partition diagram for understanding the lipophilicity of the topotecan drug species. The well-defined voltammetric characteristics for topotecan transfer in pH 4.0 buffer was then employed in conjunction with a microhole supported water/polyvinyl chloride-2-nitrophenyloctyl ether (PVC-NPOE) gel interface to develop a topotecan sensor. Current responses due to the direct transfer of topotecan molecules across the microhole interface increased linearly with respect to topotecan concentration when using cyclic voltammetry and differential pulse stripping voltammetry (DPSV). Improvements in sensitivity were obtained using DPSV and preconcentrating topotecan in the gel layer by holding the transferring potential at 1 V (vs Ag/AgCl) for 30 s followed by stripping of the drug. The topotecan drug sensor shows a low detectable concentration of 0.1 mu M with a good selectivity over other anticancer drug molecules and interfering reagents. As a practical demonstration, the sensing platform was applied for the analysis of topotecan in a diluted serum sample. The results were also compared to those using high performance liquid chromatography (HPLC).

Abstract The results of a. systematic molecular dynamics study of the interfacial structure between the gold (100) surface and two room-temperature ionic liquids, namely, 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIm][PF6]) and 1-butyl-3-methylimadazolium bis(trifluoromethylsulfonyl)imide ([BMIm][NTf2]), are herein reported. It is found that near an uncharged surface the IL structure differs from its bulk, having an enhanced density extended until the two first layers. Interfacial layering is clearly observed at the gold surface, with a higher effect for the [BMIm][NTf2] IL but a higher packing for [BMIm][PF6]. In both ILs the alkyl side chains are oriented parallel to the interface while the imidazolium rings tend to be parallel to the interface in about 60% of the cases. The presence of the interface has a higher impact on the orientation of the cations than on the chemical properties of the counterion. The surface potential drop across the interface is more pronounced toward a negative value for ([BMIm][PF6]) than for ([BMIm][NTf2]), due to relatively larger local density of the anions for ([BMIm][PF6]) near the gold surface.

Abstract MK2 (or MAPKAPK2) was already known for its role in the inflammatory response, however recent studies indicate the involvement of this protein kinase in the DNA damage response mechanism. Within its kinase family the enzyme MK3 shows the highest identity with MK2. Here we report a theoretical study on the binding of two molecules, 05B and P4O, to the proteins MK2 and MK3. The data here obtained may shed light on the contribution of individual residues and binding site water molecules for the binding of potential inhibitors to these two kinases.