Publications

Abstract Photodynamic therapy (PDT) is an anticancer therapeutic modality with remarkable advantages over more conventional approaches. However, PDT is greatly limited by its dependence on external light sources. Given this, PDT would benefit from new systems capable of a light-free and intracellular photodynamic effect. Herein, we evaluated the heavy-atom effect as a strategy to provide anticancer activity to derivatives of coelenterazine, a chemiluminescent single-molecule widespread in marine organisms. Our results indicate that the use of the heavy-atom effect allows these molecules to generate readily available triplet states in a chemiluminescent reaction triggered by a cancer marker. Cytotoxicity assays in different cancer cell lines showed a heavy-atom-dependent anticancer activity, which increased in the substituent order of hydroxyl < chlorine < bromine. Furthermore, it was found that the magnitude of this anticancer activity is also dependent on the tumor type, being more relevant toward breast and prostate cancer. The compounds also showed moderate activity toward neuroblastoma, while showing limited activity toward colon cancer. In conclusion, the present results indicate that the application of the heavy-atom effect to marine coelenterazine could be a promising approach for the future development of new and optimized self-activating and tumor-selective sensitizers for light-free PDT.

Abstract Osteoporosis therapies leveraging bisphosphonates and mineral components (e.g., magnesium, calcium, and strontium) have been raising attention because of their potential for managing this ever-growing disease. The administration of multicomponent therapeutics (combined therapy) in elderly patients is complex and suffers from low patient adherence. Herein, we report an all-in-one combination of four antiosteoporotic components into a new family of coordination complexes: [M-2(H(4)alen)(4)(H2O)(2)]center dot 1.5H(2)O [where M2+ = Mg2+ (1), (Mg0.535Ca0.465)(2+) (2) and (Mg0.505Ca0.450Sr0.045)(2+) (3)]. These solid-state complexes were prepared, for the first time, through microwave-assisted synthesis. It is demonstrated that the compounds are capable of releasing their antiosteoporotic components, both in conditions that mimic the path along the gastrointestinal tract and in long periods under physiological conditions (pH similar to 7.4). More importantly, when administered in low concentrations, the compounds did not elicit a cytotoxic effect toward liver, kidney, and osteoblast-like cell lines. Besides, it is important to highlight the unique coordination complex with four bone therapeutic components, [(Mg0.505Ca0.450Sr0.045)(2)(H(4)alen)(4)(H2O)(2)]center dot 1.5H(2)O (3), which significantly promoted osteoblast metabolic activity up to ca. 1.4-fold versus the control group. These findings bring this type of compounds one-step closer to be considered as an all-in-one and more effective treatment for managing chronic bone diseases, prompting further research on their therapeutic properties.

Abstract <jats:p>Carbon dots (CDs) are fluorescence carbon-based nanomaterials that possess several properties such as photoluminescence, biocompatibility and good water solubility. They can be fabricated from a large variety of precursors; however, most available organic molecules are still expensive and their use or synthesis can lead to significant challenges to the environment and human health. It has become desirable to use biomass waste as alternative precursors in the synthesis of CDs, given that biomass waste material is ubiquitous, nontoxic, cheap and renewable. Spent coffee grounds (SCGs) are the residues of the treatment of coffee powder can be a potential carbon source to a more environmentally sustainable synthesis route. In this work, we fabricated SCG-based CDs via one-pot and solvent-free carbonization at 200 °C of solid samples generating particles with sizes between 2.1 and 3.9 nm. These carbon nanoparticles exhibited blue fluorescence and excitation-dependent emission of carbon dots with moderate quantum yields (2.9–5.8%). The presence of heavy metals in water resources, such as Fe3+, can lead to adverse health effects. SCG-based CDs showed potential for being used as optical Fe3+ optical sensors, with Life Cycle Assessment (LCA) studies validating the SCGs as more sustainable precursors than classical precursors, both considering a weight- or function-based functional unit.</jats:p>

Abstract Ionic liquids (ILs) are remarkable chemical compounds with applications in many areas of modern science. They are increasingly recognized as promising compounds to fight microorganisms in both planktonic and biofilm states, contributing to reinvent the antimicrobial pipeline. Biofilm-related infections are particularly challenging given that the scientific community has not yet identified a reliable control strategy. Understanding of the action of ILs in biofilm control is is still in a very early stage. However, given the highly tunable nature and exceptional properties of ILs, they are excellent candidates for biofilm control. Here, we review the major advances in, and challenges tothe use of ILs for effective biofilm control.

Abstract Computer-aided design of new drugs is an exponentially growing field, especially in the last decade. The support of theoretical tools may accelerate the drug discovery process, which is a long and very expensive journey. Tools as QSAR and docking calculations are on the top of the list for helping medicinal chemists to find more potent and selective molecules as potential leads for facing challenging diseases. Coumarins have been an important source of inspiration for the design of new drugs. Due to their chemical properties and their affinity to some targets, special attention has been paid to their role against neurodegenerative diseases. Therefore, the authors provide an overview of the scientific reports describing the research and development of new drug design tools supporting the discovery of coumarins as enzymatic inhibitors or receptor ligands involved in these diseases. This review emphasizes the rationale behind the design of new drug candidates, and particular attention is paid to the search for new leads over the last 10 years. QSAR and docking studies are discussed, as well as new technologies applied for the research in this field. The manuscripts discussed in this review have been collected from multiple electronic databases, including Pubmed, SciFinder, and Mendeley.

Abstract Here we report the rational development of a carbon dot (CDs)-based fluorescent pH nanosensor by employing an active surface preservation strategy. More specifically, citric acid, urea and fluorescein were subjected to a one-pot hydrothermal treatment, which preserved fluorescein-like structures on the surface of the CDs. The obtained CDs showed pH-sensitive green emission, which can be used to determine pH variations from 3.7 to 12.1 by fluorescence enhancement. Moreover, the obtained nanoparticles showed excellent selectivity toward pH, fluorescence reversibility in different pH values, photostability, while being compatible with human cell lines (even at high concentrations). Furthermore, their performance as pH sensors was comparable with reference pH determination procedures. Thus, an active surface preservation strategy was successfully employed to develop fluorescence pH nanosensors in a rational manner and without post-synthesis functionalization strategies, which show potential for future use in pH determination.

Abstract Mitochondriotropic antioxidants (MC3, MC6.2, MC4 and MC7.2) based on dietary antioxidants and analogs (caffeic, hydrocaffeic, trihydroxyphenylpropanoic and trihydroxycinnamic acids) were developed. In this study, we evaluate and compare the cytotoxicity profile of novel mitochondria-targeted molecules (generally known as MitoCINs) on human HepG2 and differentiated SH-SY5Y cells with the quinone-based mitochondria-targeted antioxidants MitoQ and SkQ(1) and with two non-targeted antioxidants, resveratrol and coenzyme Q(10) (CoQ(10)). We further evaluate their effects on mitochondrial membrane potential, cellular oxygen consumption and extracellular acidification rates. Overall, MitoCINs derivatives reduced cell viability at concentrations about six times higher than those observed with MitoQ and SkQ1. A toxicity ranking for both cell lines was produced: MC4 < MC7.2 < MC3 < MC6.2. These results suggest that C-6 carbon linker and the presence of a pyrogallol group result in lower cytotoxicity. MC3 and MC6.2 affected the mitochondrial function more significantly relative to MitoQ, SkQ1, resveratrol and CoQ(10), while MC4 and MC7.2 displayed around 100-1000 times less cytotoxicity than SkQ1 and MitoQ. Based on the mitochondrial and cytotoxicity cellular data, MC4 and MC7.2 are proposed as leads that can be optimized to develop safe drug candidates with therapeutic application in mitochondrial oxidative stress-related diseases.

Abstract The electrochemical behaviour of the alkaloids berberine and palmatine at the polarized water/1,2-dichloroethane interface is studied by first time. The interface is supported on the micropores of a PET (polyethylene terephthalate) membrane by using an electrochemical cell employed in previous works. Chronoamperometry and square wave voltammetry are applied in order to determine the concentrations of the ions berberine and palmatine in water. Thus, calibration curves are built with both techniques and the resulting detection limits are discussed and compared. In addition, the chronoamperograms and square wave voltammograms recorded are used to estimate the standard transfer potentials and the aqueous diffusion coefficients for the two cations. The diffusion coefficient values are further compared with results of molecular dynamic simulations, finding a good correlation between experimental and simulated data.

Abstract The design and synthesis of artificial receptors based on molecular imprinting (MI) technology for the development of a new MIP-based biosensor for detection of the stress biomarker α-amylase in human saliva in point-of-care (PoC) applications is described in this work. The portable electrochemical devices for monitoring α-amylase consists of cost-effective and disposable gold screen-printed electrodes (AuSPEs). To build the electrochemical device, the template biomolecule was firstly immobilized directly over the working area of the gold chip previously activated with a self-assembled monolayer (SAM) of cysteamine (CA). Then, pyrrole (Py) monomer was selected as building block of a polymeric network prepared by CV electropolymerization. After the electropolymerization process, the enzyme was removed from the polymer film in order to build the specific recognition sites for the target enzyme. The MIP biosensor showed a very wide linear concentration range (between 3.0 × 10−4 to 0.60 mg mL−1 in buffer solution and between 3.0 × 10−4 to 3.0 × 10−2 mg mL−1 in human saliva) and low detection levels were achieved (LOD < 3.0 × 10−4 mg mL−1) using square wave voltammetry (SWV) as the electroanalytical technique.