Publications

Abstract The main etiological agents in dermatophytosis of human skin and nails are Trichophyton, in particular Trichophyton rubrum (T. rubrum) and Trichophyton mentagrophytes (T. mentagrophytes). A new series of twenty-three 3- and 4-arylcoumarins was synthesized and the antifungal activities against clinical isolates of T. rubrum and T. mentagrophytes were evaluated. Sixteen out of twenty-three molecules exhibited antifungal activity against one or both fungi strains. In some cases, the activity against T. rubrum has been comparable to fluconazole, one of the standards, being 8-methoxy-3-(4'-nitrophenyl)coumarin (16) the best compound within this series (minimum inhibitory concentration, MIC=6.25 mu g/mL). The preliminary structure-activity relationship study showed that the antifungal activity depends on the position and nature of the substitution patterns. The cytotoxicity of eleven compounds on D-384 (astrocytoma), A-549 (lung cancer) and RKO (colorectal cancer) cell lines was also performed. With the aim of deeply understand the potential of these molecules as hits to develop new drugs, the theoretical absorption, distribution, metabolism and excretion (ADME) properties of the active compounds were calculated.

Abstract Central nervous system (CNS) diseases, such neurodegenerative disorders (NDs) are increasing over the last years as a consequence of a continuous growing of the life expectancy and aging of population. The molecular mechanisms underlying the pathophysiology of NDs are still not fully understood. Neurodegeneration seems to be multifactorial and associated to a complex set of events comprising oxidative stress, inflammation, protein dysfunction and aggregation, among others, that at the end lead to the demise of neurons. It has been advocated that oxidative stress induced by imbalanced redox states, involving either overproduction of reactive species or dysfunction of the antioxidant system, and the higher levels of iron in the brain has a crucial role in NDs progression. Therefore, antioxidant therapy emerged as a useful approach to modulate oxidative stress events. However, despite the promising results obtained in in vitro cell-free and cell-based assays, the pharmacokinetics/pharmacodynamics properties of the majority of antioxidants preclude their advance in pre- and clinical trials. In this chapter the nonenzymatic endogenous and exogenous antioxidants (single and combined antioxidant therapy) currently in clinical trials, as drugs or supplements, for treatment of NDs will be highlighted. From the data one can conclude that the clinical trials performed so far related with single or combined antioxidants are still in a very early stage. So, a huge research space in the antioxidant field remains to be explored that hopefully will yield new and effective neuroprotective agents in a foreseeable future.

Abstract Oxidative stress is characterized by an imbalanced redox state that is principally related with a plethora of radical reactions skilled to trigger several pathophysiological mechanisms. So, the antioxidant therapy based on uptake of exogenous dietary antioxidants emerged as a useful approach to modulate the progression of oxidative stress-related events. Among dietary antioxidants, promising results have been obtained in in vitro cell-free and cell-based assays for huperzine A, α-lipoic acid, vitamins C and E, resveratrol, curcumin, epigallocatechin-3-gallate, and phenolic acids. However, the lack of drug-like pharmacokinetic properties precludes their advance in pre-and clinical trials. Although some dietary antioxidants, such as huperzine A, α-lipoic acid, resveratrol, and quercetin, were described to be able to surpass the blood-brain barrier, they have not been approved yet. Thus, new strategies have emerged by means of central chemical modifications or the use of nanoplatforms, along with new administration routes, which can facilitate their delivery across the blood-brain barrier.

Abstract Although Solanum nigrum L. is a phytoremediator for different metals, its growth and physiology are still compromised by toxic levels of zinc (Zn). Thus, the development of eco-friendly strategies to enhance its tolerance, maintaining remediation potential is of special interest. This study evaluated the potential of 24-epibrassinolide (24-EBL) to boost S. nigrum defence against Zn towards a better growth rate and remediation potential. After 24 days of exposure, the results revealed that Zn-mediated inhibitory effects on biomass and biometry were efficiently mitigated upon application of 24-EBL, without affecting Zn accumulation. The evaluation of oxidative stress markers reported that Zn excess stimulated the accumulation of superoxide anion (O-2(center dot-)), but reduced hydrogen peroxide (H2O2) levels, while not altering lipid peroxidation (LP). This was accompanied by an up-regulation of the antioxidant system, especially proline, superoxide dismutase (SOD) and ascorbate peroxidase (APX) in both organs, and ascorbate in roots of Zn-exposed plants. Foliar application of 24-EBL, however, induced distinctive effects, lowering proline levels in both organs, as well as APX activity in shoots and SOD in roots, whilst stimulating GSH and total thiols in both organs, as well as SOD and APX activity, in shoots and in roots, respectively. Probably due to a better antioxidant efficiency, levels of O-2(center dot-) and H2O2 in pre-treated plants remained identical to the control, while LP further decreased in shoots. Overall, our results indicate a protective effect of 24-EBL on S. nigrum response to excess Zn, contributing for a better tolerance and growth rate, without disturbing its phytoremediation potential.

Abstract In this Letter, we report the first observation of the capacitance-potential hysteresis at the ionic liquid vertical bar electrode interface in atomistic molecular dynamics simulations. While modeling the differential capacitance dependence on the potential scan direction, we detected two long-living types of interfacial structure for the BMImPF(6) ionic liquid at specific charge densities of the gold Au(111) surface. These structures differ in how counterions overscreen the surface charge. The high barrier for the transition from one structure to another slows down the interfacial restructuring process and leads to the marked capacitance-potential hysteresis.

Abstract <jats:p>Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of editorials which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...]</jats:p>

Abstract The goal of this research was to evaluate the procedures of the Discursive Textual Analysis implemented in a handcrafted manner or assisted by the IRAMUTEQ software in order to identify analytical convergences and/or divergences. The theme was the expectations of young students from military colleges in Rio Grande do Sul (Brazil). Participants were High School students (n = 7). The data collection instrument was the semi-structured interview. The data analysis method was the Discursive Textual Analysis, both in a handcrafted manner and assisted by the IRAMUTEQ software. The main result was the convergence of 62% between both ways to generate categories. The convergences and divergences between the procedures of the Discursive Textual Analysis method presented satisfactory parameters for the context of the research and the interpretative assumptions of qualitative research.

Abstract The structure of the title quinoline carboxamide derivative, C26H25N3O, is described. The quinoline moiety is not planar as a result of a slight puckering of the pyridine ring. The secondary amine has a slightly pyramidal geometry, certainly not planar. Both intra- and intermolecular hydrogen bonds are present. Hirshfeld surface analysis and lattice energies were used to investigate the intermolecular interactions.

Abstract A study on the Pb(II) imprinting performed within mesoporous sulphated biopolymer/siloxane composites, prepared in media containing deep eutectic solvent (DES), is described. In general, the process of imprinting resulted in greatly increased surface areas relatively to the corresponding nonimprinted composites [up to fivefold (from 76 m(2) g(-1) to 360 m(2) g(-1)) for fucoidan (Fuc) and up to twofold (from 208 m(2) g(-1) to 351 m(2) g(-1)) for chondroitin sulfate (CS) composites], the diminishing of mean pore size (from 3.3-4.6 nm to 2.9-3.4), and higher biopolymer contents (from mass fractions of 0.42-0.52 to 0.46-0.68). The sorption features depended a great deal on the biopolymer/DES combination. The best CS composite, allowed for 12% capacity and 20% binding strength, as well as Pb(II)/Cd(II) selectivity enhancements. The largest of the capacities was obtained with the imprinted Fuc/DES-E composite, 86 mg g(-1), a 10% increase. Concerning the selectivity [Pb(II) versus Cd(II)], there was a significant increase for the CS composites (from 1.0-1.1 (alpha(qmax))/1.1-1.2 (alpha(K)) to 1.3-1.4 (alpha(qmax))/1.3-1.6 (alpha(K))]. In particular, the DES-E CIC presented high selectivity factors (alpha(qmax) 3.0/alpha(K) 3.2) in line with those of the microporous version (alpha(qmax) 2.0/alpha(K) 3.3) but showing a significant increase in terms of the alpha(qmax) selectivity. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48842.