Percorrer por autor "Branco, Luís C."
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- Alendronic Acid as Ionic Liquid: New Perspective on OsteosarcomaPublication . Teixeira, Sónia; Santos, Miguel M.; Fernandes, Maria H.; Costa-Rodrigues, Joao; Branco, Luís C.Herein the quantitative synthesis of eight new mono- and dianionic Organic Salts and Ionic Liquids (OSILs) from alendronic acid (ALN) is reported by following two distinct sustainable and straightforward methodologies, according to the type of cation. The prepared ALN-OSILs were characterized by spectroscopic techniques and their solubility in water and biological fluids was determined. An evaluation of the toxicity towards human healthy cells and also human breast, lung and bone (osteosarcoma) cell lines was performed. Globally, it was observed that the monoanionic OSILs showed lower toxicity than the corresponding dianionic structures to all cell types. The highest cytotoxic effect was observed in OSILs containing a [C2OHMIM] cation, in particular [C2OHMIM][ALN]. The latter showed an improvement in IC50 values of ca. three orders of magnitude for the lung and bone cancer cell lines as well as fibroblasts in comparison with ALN. The development of OSILs with high cytotoxicity effect towards the tested cancer cell types, and containing an anti-resorbing molecule such as ALN may represent a promising strategy for the development of new pharmacological tools to be used in those pathological conditions.
- Antibacterial activity of ionic liquids based on betalactamantibiotics against resistant bacteriaPublication . Dias, Vitorino; Santos, Miguel; Prudêncio, Cristina; Noronha, João P.; Grilo, Inês R.; Sobral, Rita G.; Dias, Ana Rita; Branco, Luís C.; Ferraz, RicardoThe cases of antibiotic resistance are increasing and becoming more and more common, giving rise to a new problem for public health. Therefore, the discovery of new antibiotics is important and necessary.
- Antitumor Activity of Ionic Liquids Based on AmpicillinPublication . Ferraz, Ricardo; Costa-Rodrigues, Joao; Fernandes, Maria H.; Santos, Miguel M.; Marrucho, Isabel M.; Rebelo, Luís Paulo N.; Prudêncio, Cristina; Noronha, João Paulo; Petrovski, Željko; Branco, Luís C.Significant antiproliferative effects against various tumor cell lines were observed with novel ampicillin salts as ionic liquids. The combination of anionic ampicillin with appropriate ammonium, imidazolium, phosphonium, and pyridinium cations yielded active pharmaceutical ingredient ionic liquids (API-ILs) that show potent antiproliferative activities against five different human cancer cell lines: T47D (breast), PC3 (prostate), HepG2 (liver), MG63 (osteosarcoma), and RKO (colon). Some API-ILs showed IC50 values between 5 and 42 nm, activities that stand in dramatic contrast to the negligible cytotoxic activity level shown by the ampicillin sodium salt. Moreover, very low cytotoxicity against two primary cell lines—skin (SF) and gingival fibroblasts (GF)—indicates that the majority of these API-ILs are nontoxic to normal human cell lines. The most promising combination of antitumor activity and low toxicity toward healthy cells was observed for the 1-hydroxyethyl-3-methylimidazolium–ampicillin pair ([C2OHMIM][Amp]), making this the most suitable lead API-IL for future studies.
- Bioactivity of ionic liquids based on valproate in SH-SY5Y human neuroblastoma cell linePublication . Dias, Ana Rita; Ferraz, Ricardo; Costa-Rodrigues, João; Santos, Andreia F. M.; Jacinto, Manuel L.; Prudêncio, Cristina; Noronha, João Paulo; Branco, Luís C.; Petrovsk, ŽeljkoThe search for alternative and effective therapies to fight cancer is one of the main goals of the pharmaceutical industry. Recently, ionic liquids (ILs) have emerged as potential therapeutic agents with antitumor properties. The goal of this study was to synthesize and evaluate the bioactivity of different ILs coupled with the active pharmaceutical ingredient (API) valproate (VPA) as an antitumor agent. The toxicity of the prepared ionic liquids was evaluated by the MTT cell metabolic assay in human neuroblastoma SH-SY5Y and human primary Gingival Fibroblast (GF) cell lines, in which they showed inhibitory effects during the study period. In addition, low cytotoxicity against GF cell lines was observed, suggesting that these compounds are not toxic to human cell lines. [C2OHDMiM][VPA] demonstrated an outstanding antitumor activity against SH-SY5Y and lower activity against the non-neoplastic GF line. The herein assessed compounds played an important role in the modulation of the signaling pathways involved in the cellular behavior. This work also highlights the potential of these ILs-API as possible antitumor agents.
- Bioactivity of ionic liquids based on valproate in the human osteoclastogenesisPublication . Correia, Joana; Ferraz, Ricardo; Costa-Rodrigues, João; Fernandes, Maria Helena; Branco, Luís C.; Noronha, João Paulo; Petrovski, eljko; Prudêncio, CristinaIonic Liquids (ILs) are salts (with at least one organic cation), that have a melting point lower than 100º C. The interest in these compounds has been increasing as well as the number of applications where they can be used. Their first applications were on batteries and in organic synthesis and soon they started to be applied on health sciences. With this work we intend to study the biological properties of ILs based on valproate, and evaluate their modulation potential on human osteoclastogenesis.
- Biological activity of ionic liquids based on bis-pyridinium in Gram-positive and Gram- negative bacteriaPublication . Ferreira, Joana; Ferraz, Ricardo; Vieira, Mónica; Fernandes, Rúben; Branco, Luís C.; Noronha, João Paulo; Petrovski, eljko; Prudêncio, CristinaResistance to antibiotics is becoming a public health problem and is the subject of concern from various global entities. In this context, finding new alternatives to combat microbial infections is critical. Ionic liquids (ILs) come up as a resource to be used in the pharmaceutical industry, especially in the synthesis of new antibiotics. The ILs have shown the ability to improve the characteristics of active pharmaceutical ingredients. However this is not the only the relevance of these compounds, antimicrobial properties also have been described. The bis-pyridinium ILs are now being studied as antimicrobial agents in the present study.
- Etidronate-based organic salts and ionic liquids: In vitro effects on bone metabolismPublication . Teixeira, Sónia; Santos, Miguel M.; Branco, Luís C.; Costa-Rodrigues, JoãoBisphosphonates are a class of drugs widely used for the treatment of several pathologies associated with increased bone resorption. Although displaying low oral bioavailability, these drugs have the ability to accumulate in bone matrix, where the biological effects are exerted. In the present work, four mono- and dianionic Etidronate-based Organic Salts and Ionic Liquids (Eti-OSILs) were developed by combination of this drug with the superbases 1,1,3,3-tetramethylguanidine (TMG) and 1,5-diazabicyclo(4.3.0)non-5-ene (DBN) as cations, aiming to improve not only the physicochemical properties of this seminal bisphosphonate, but also its efficacy in the modulation of cellular behavior, particularly on human osteoclasts and osteoblasts. It was observed that some of the developed compounds, in particular the dianionic ones, presented very high water solubility and diminished or absent polymorphism. Also, several of them appeared to be more cytotoxic against human breast and osteosarcoma cancer cell lines while retaining low toxicity to normal cells. Regarding bone cells, a promotion of an anabolic state was observed for all Eti-OSILs, primarily for the dianionic ones, which leads to an inhibition of osteoclastogenesis and an increase in osteoblastogenesis. The observed effects resulted from differential modulation of intracellular signaling pathways by the Eti-OSILs in comparison with Etidronate. Hence, these results pave the way for the development of more efficient and bioavailable ionic formulations of bisphosphonates aiming to effectively modulate bone metabolism, particularly in the case of increased bone resorption.
- Ionic Liquids – From organic solvents to pharmaceutical applicationsPublication . Ferraz, Ricardo; Costa-Rodrigues, João; Fernandes, Maria Helena; Branco, Luís C.; Noronha, João Paulo; Petrovski, Eljko; Fernandes, Rúben; Prudêncio, CristinaIonic liquids are compounds that have melting temperature below 100ºC and they have been evolved from traditional high temperature molten salts.. The quest for useful molten salts with lower melting temperatures led to inorganic chloroaluminates, to organic chloroaluminates and to organic salts now being developed for green chemistry applications and recently has been a major emphasis placed on ionic liquids as bearers of desired biological activity.
- Ionic liquids as active pharmaceutical ingredientsPublication . Ferraz, Ricardo; Branco, Luís C.; Prudêncio, Cristina; Noronha, João Paulo; Petrovski, ŽeljkoIonic liquids (ILs) are ionic compounds that possess a melting temperature below 100 °C. Their physical and chemical properties are attractive for various applications. Several organic materials that are now classified as ionic liquids were described as far back as the mid-19th century. The search for new and different ILs has led to the progressive development and application of three generations of ILs: 1) The focus of the first generation was mainly on their unique intrinsic physical and chemical properties, such as density, viscosity, conductivity, solubility, and high thermal and chemical stability. 2) The second generation of ILs offered the potential to tune some of these physical and chemical properties, allowing the formation of “task-specific ionic liquids” which can have application as lubricants, energetic materials (in the case of selective separation and extraction processes), and as more environmentally friendly (greener) reaction solvents, among others. 3) The third and most recent generation of ILs involve active pharmaceutical ingredients (API), which are being used to produce ILs with biological activity. Herein we summarize recent developments in the area of third-generation ionic liquids that are being used as APIs, with a particular focus on efforts to overcome current hurdles encountered by APIs. We also offer some innovative solutions in new medical treatment and delivery options.
- A Novel Approach for Bisphosphonates: Ionic Liquids and Organic Salts from Zoledronic AcidPublication . Teixeira, Sónia; Santos, Miguel M.; Ferraz, Ricardo; Prudêncio, Cristina; Fernandes, Maria H.; Costa-Rodrigues, Joao; Branco, Luís C.Novel ionic liquids and organic salts based on mono- or dianionic zoledronate and protonated superbases, choline and n-alkylmethylimidazolium cations, were prepared and characterized by spectroscopic and thermal analyses. Most of the prepared salts display amorphous structures and very high solubility in water and saline solutions, especially the dianionic salts. Among the zoledronate-based ionic compounds, those containing choline [Ch] and methoxyethylmethylimidazolium [C3 OMIM] cations appear to have significant cytotoxicity against human osteosarcoma cells (MG63) and low toxicity toward healthy skin fibroblast cells. Because osteosarcoma is a bone pathology characterized by an increase in bone turnover rate, the results presented herein may be a promising starting point for the development of new ionic pharmaceutical drugs against osteosarcoma.