Browsing by Author "Fernandes, Maria Helena"
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- Antiproliferative organic salts derived from betulinic acid: Disclosure of an ionic liquid selective against lung and liver cancer cellsPublication . Silva, Ana Teresa; Cerqueira, Maria João; Prudêncio, Cristina; Fernandes, Maria Helena; Costa-Rodrigues, João; Teixeira, Cátia; Gomes, Paula; Ferraz, RicardoIn the last few years, we have been witnessing an increasing interest in ionic liquids (ILs) and organic salts, given their potential applications in biological and pharmaceutical sciences. We report the synthesis and in vitro evaluation of novel organic salts combining betulinate, known for its anticancer properties, with antimalarial drugs, primaquine, chloroquine, and mepacrine, and also with the trihexyltetradecylphosphonium ([P6,6,6,14]) cation. The salts were screened for their in vitro activity against tumor lines HepG2 (liver), MG63 (osteosarcoma), T47D (breast), A459 (lung), and RKO (colon), and also on normal human fibroblasts. All betulinates prepared displayed antiproliferative properties, with the trihexyltetradecylphosphonium betulinate standing out for its higher selectivity. This unprecedented disclosure of a betulinic acid (BA)-derived IL with selective antitumor activity constitutes a relevant first step toward development of novel anticancer therapies based on BA-derived IL.
- 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.
- Characterization of cellular and molecular effects of lycopene on human bone cellsPublication . Costa-Rodrigues, João; Fernandes, Maria Helena; Pinho, Olívia; Monteiro, PedroBone is a dynamic tissue that undergoes continuous remodeling. This process is modulated by numerous factors, among which is oxidative stress. Mainly due to its high antioxidant potential, lycopene has been linked to a decreased risk of some chronic diseases, including osteoporosis, but the characterization of lycopene effects on bone tissue remains to be elucidated.
- Cytotoxicity in L929 fibroblasts and inhibition of herpes simplex virus type 1 Kupka by estuarine cyanobacteria extractsPublication . Lopes, Viviana R.; Schmidtke, Michaela; Fernandes, Maria Helena; Martins, Rosario; Vasconcelos, VítorThe cyanobacteria are known to be a rich source of metabolites with a variety of biological activities in different biological systems. In the present work, the bioactivity of aqueous and organic (methanolic and hexane) crude extracts of cyanobacteria isolated from estuarine ecosystems was studied using different bioassays. The assessment of DNA damage on the SOS gene repair region of mutant PQ37 strain of Escherichia coli was performed. Antiviral activity was evaluated against influenza virus, HRV-2, CVB3 and HSV-1 viruses using crystal violet dye uptake on HeLa, MDCK and GMK cell lines. Cytotoxicity evaluation was performed with L929 fibroblasts by MTT assay. Of a total of 18 cyanobacterial isolates studied, only the crude methanolic extract of LEGE 06078 proved to be genotoxic (IF > 1.5) in a dose-dependent manner and other four were putative candidates to induce DNA damage. Furthermore, the crude aqueous extract of LEGE 07085 showed anti- herpes type 1 activity (IC50 = 174.10 μg dry extract mL−1) while not presenting any cytotoxic activity against GMK cell lines. Of the 54 cyanobacterial extracts tested, only the crude methanolic and hexane ones showed impair on metabolic activity of L929 fibroblasts after long exposure (48–72 h). The inhibition of HSV-1 and the strong cytotoxicity against L929 cells observed emphasizes the importance of evaluating the impact of those estuarine cyanobacteria on aquatic ecosystem and on human health. The data also point out their potential application in HSV-1 treatment and pharmacological interest.
- Differential effects of antiepileptic drugs on human bone cellsPublication . Rocha, Sara; Ferraz, Ricardo; Prudêncio, Cristina; Fernandes, Maria Helena; Costa-Rodrigues, JoaoAntiepileptic drugs (AED) have been associated to in vivo deleterious consequences in bone tissue. The present work aimed to characterize the cellular and molecular effects of five different AED on human osteoclastogenesis and osteblastogenesis. It was observed that the different drugs had the ability to differentially modulate both processes, in a way dependent on the identity and dose of the AED. Shortly, valproic acid stimulated either osteoclastogenesis and osteoblastogenesis, whereas carbamazepine, gabapentin, and lamotrigine revealed an opposite behavior; topiramate elicited a decrease of osteoclast development and an increase in osteoblast differentiation. This is the first report describing the direct effects of different AED on human primary bone cells, which is a very important issue, because these drugs are usually consumed in long-term therapeutics, with acknowledged in vivo effects in bone tissue.
- Etidronate-based ionic liquids: in vitro effects on bone metabolismPublication . Teixeira, Sónia; Santos, Miguel; Branco, Luís; Fernandes, Maria Helena; Costa-Rodrigues, JoãoThe Bisphosphonates have been used for various purposes since the middle of the 19th century, but the propriety that elicited more curiosity was their ability to regulate bone mineralization. This characteristic made this drug the elite choice for treatments of several pathologies associated to increased bone resorption.
- Exploring bioactive properties of marine cyanobacteria Isolated from the Portuguese coast: high potential as a source of anticancer compoundsPublication . Costa, Margarida; Garcia, Mónica; Costa-Rodrigues, Joao; Costa, Maria Sofia; Ribeiro, Maria João; Fernandes, Maria Helena; Barros, Piedade; Barreiro, Aldo; Vasconcelos, Vítor; Martins, RosarioThe oceans remain a major source of natural compounds with potential in pharmacology. In particular, during the last few decades, marine cyanobacteria have been in focus as producers of interesting bioactive compounds, especially for the treatment of cancer. In this study, the anticancer potential of extracts from twenty eight marine cyanobacteria strains, belonging to the underexplored picoplanktonic genera, Cyanobium, Synechocystis and Synechococcus, and the filamentous genera, Nodosilinea, Leptolyngbya, Pseudanabaena and Romeria, were assessed in eight human tumor cell lines. First, a crude extract was obtained by dichloromethane:methanol extraction, and from it, three fractions were separated in a Si column chromatography. The crude extract and fractions were tested in eight human cancer cell lines for cell viability/toxicity, accessed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactic dehydrogenase release (LDH) assays. Eight point nine percent of the strains revealed strong cytotoxicity; 17.8% showed moderate cytotoxicity, and 14.3% assays showed low toxicity. The results obtained revealed that the studied genera of marine cyanobacteria are a promising source of novel compounds with potential anticancer activity and highlight the interest in also exploring the smaller filamentous and picoplanktonic genera of cyanobacteria.
- 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.
- Marine cyanobacteria compounds with anticancer properties: a review on the implication of apoptosisPublication . Costa, Margarida; Costa-Rodrigues, Joao; Fernandes, Maria Helena; Barros, Piedade; Vasconcelos, Vítor; Martins, RosarioMarine cyanobacteria have been considered a rich source of secondary metabolites with potential biotechnological applications, namely in the pharmacological field. Chemically diverse compounds were found to induce cytoxicity, anti-inflammatory and antibacterial activities. The potential of marine cyanobacteria as anticancer agents has however been the most explored and, besides cytotoxicity in tumor cell lines, several compounds have emerged as templates for the development of new anticancer drugs. The mechanisms implicated in the cytotoxicity of marine cyanobacteria compounds in tumor cell lines are still largely overlooked but several studies point to an implication in apoptosis. This association has been related to several apoptotic indicators such as cell cycle arrest, mitochondrial dysfunctions and oxidative damage, alterations in caspase cascade, alterations in specific proteins levels and alterations in the membrane sodium dynamics. In the present paper a compilation of the described marine cyanobacterial compounds with potential anticancer properties is presented and a review on the implication of apoptosis as the mechanism of cell death is discussed.
- Modulation of human osteoclastogenesis and osteoblastogenesis by lycopenePublication . Costa-Rodrigues, João; Fernandes, Maria Helena; Pinho, Olívia; Monteiro, PedroLycopene is a lipid-soluble pigment that is mainly found in tomato. It is the carotenoid that presents the highest antioxidant potential, and due to that, it has been implicated in a decrease of the risk of several oxidative-stress-related disorders, such as cancer, inflammatory diseases and osteoporosis. Nevertheless, at the present, there is no detailed information about how lycopene affects bone metabolism. The aim of the present work was to characterize the cellular and molecular effects of lycopene on human osteoclast and osteoblast differentiation and function. It was observed that lycopene, at levels found in plasma after the ingestion of lycopene-containing products, decreased osteoclast differentiation but did not affect cell density/survival; calcium-phosphate resorbing ability was also decreased. On the other hand, osteoblast proliferation (via a decrease on apoptosis) and differentiation were increased in the presence of lycopene. The observed effects in both cell types appeared to be related to significant changes in MEK signaling pathway, but also in protein kinase C pathway in osteoclasts and NFkB signaling in osteoblasts. In conclusion, lycopene appears to promote an anabolic state of bone metabolism, stimulating osteoblastogenesis and inhibiting osteoclastogenesis, which may contribute to the promotion of a proper health status of bone tissue. This information might be relevant for the prevention and delay in the progression of osteolytic bone conditions.