30 documents found, page 1 of 3
Prediction of terpenoid toxicity based on a quantitative structure–activity rel...
Perestrelo, Rosa; Silva, Catarina; Fernandes, Miguel X.; Câmara, José S.Terpenoids, including monoterpenoids (C10), norisoprenoids (C13), and sesquiterpenoids (C15), constitute a large group of plant-derived naturally occurring secondary metabolites with highly diverse chemical structures. A quantitative structure–activity relationship (QSAR) model to predict terpenoid toxicity and to evaluate the influence of their chemical structures was developed in this study by assessing in re...
A small molecule tubulin depolymerizing agent identified by a phenotypic drug d...
Ríos-Luci, Carla; Díaz-Rodríguez, Elena; Buey, Ruben M.; Sousa, Inês J.; Fernandes, Miguel X.; Pandiella, Atanasio; Padrón, José M.In the scenario of drug discovery, numerous in vitro testing initiatives had been established. Thus far, no general methodology is reputable and literature on this hot topic is scarce. In this respect, we propose a strategy based on a Phenotypic Drug Discovery approach. Within our program directed at the discovery of new antitumor agents, we have focused our attention on compounds that disturb the cell cycle. O...
Differential mechanism of action of the CK1ε inhibitor GSD0054
Lagunes, Irene; Martín-Batista, Elva; Silveira-Dorta, Gaston; Fernandes, Miguel X.; Padrón, José M.In the current study, we explored for the first time, the mechanism of action of the new Casein kinase 1 ε (CK1ε) selective inhibitor GSD0054. Although GSD0054 behaved as a selective CK1ε inhibitor in enzymatic assays, we studied whether this inhibitory activity also occurred inside the cells. The effects of GSD0054 on β-catenin expression and disruption of cell cycle progression were studied in the human breas...
Phosphorylation of mineralocorticoid receptor ligand binding domain impairs rec...
Jiménez-Canino, Rubén; Fernandes, Miguel X.; Alvarez de la Rosa, DiegoPost-translational modification of steroid receptors allows fine-tuning different properties of this family of proteins, including stability, activation, or interaction with co-regulators. Recently, a novel effect of phosphorylation on steroid receptor biology was described. Phosphorylation of human mineralocor ticoid receptor (MR) on Ser-843, a residue placed on the ligand binding domain, lowers affinity for a...
Caffeoylquinic acids as inhibitors for HIV-I protease and HIV-I integrase: a mo...
Serina, João C.; Castilho, Paula C.; Fernandes, Miguel X.Caffeoylquinic acids are ubiquitous phenolic compounds with several health benefits to humans and they have been shown to be promisinganti-HIV compounds. In this work, molecular docking was used to study the inhibition of HIV-I integrase and protease using caffeoylquinic acids. It was possible to establish that the naturally occurring caffeoylquinic acids are not suitable as inhibitors for protease but are very...
Dual-stage triterpenoids from an African medicinal plant targeting the malaria ...
Ramalhete, Cátia; Cruz, Filipa P. da; Mulhovo, Silva; Sousa, Inês J.; Fernandes, Miguel X.; Prudêncio, Miguel; Ferreira, Maria-José U.Sixteen triterpenoids (1–16), previously isolated from the aerial parts of the African medicinal plant Momordica balsamina or obtained by derivatization, were evaluated for their activity against liver stages of Plasmodium berghei, measuring the luminescence intensity in Huh-7 cells infected with a firefly lucif erase-expressing P. berghei line, PbGFP-Luccon. Toxicity of compounds (1–16) was assessed on the sam...
QSAR studies of macrocyclic diterpenes with P-glycoprotein inhibitory activity
Sousa, Inês J.; Ferreira, Maria-José U.; Molnár, Joseph; Fernandes, Miguel X.Multidrug resistance (MDR) represents a major limitation for cancer chemotherapy. There are several mechanisms of MDR but the most important is associated with P-glycoprotein (P-gp) overexpression. The development of modulators of P-gp that are able to re-establish drug sensitivity of resistant cells has been considered a promising approach for overcoming MDR. Macrocyclic lathyrane and jatro phane-type diterpen...
Molecular docking studies of the interaction between propargylic enol ethers an...
Silveira-Dorta, Gastón; Sousa, Inês J.; Ríos-Luci, Carla; Martín, Víctor S.; Fernandes, Miguel X.; Padrón, José M.Having identified a novel human DNA topoisomerase IIa (TOP2) catalytic inhibitor from a small and structure-focused library of propargylic enol ethers, we decided to analyze if the chirality of these compounds plays a determinant role in their antiproliferative activity. In this study, we describe for the first time the synthesis of the corresponding enantiomers and the biological evaluation against a panel of ...
Generation of artificial neural networks models in anticancer study
Sousa, Inês J.; Padrón, José M.; Fernandes, Miguel X.Artificial neural networks (ANNs) have several applications; one of them is the prediction of biological activity. Here, ANNs were applied to a set of 32 compounds with anticancer activity assayed experimentally against two cancer cell lines (A2780 and T-47D). Using training and test sets, the obtained correlation coefficients between experimental and calculated values of activity, for A2780, were 0.804 and 0.8...
Sulfated small molecules targeting EBV in Burkitt lymphoma: from in silico scre...
Lima, Raquel T.; Seca, Hugo; Palmeira, Andreia; Fernandes, Miguel X.; Castro, Felipe; Correia-da-Silva, Marta; Nascimento, Maria S. J.; Sousa, EmíliaEpstein–Barr virus (EBV) infects more than 90% of the world population. Following primary infection, Epstein– Barr virus persists in an asymptomatic latent state. Occasionally, it may switch to lytic infection. Latent EBV infection has been associated with several diseases, such as Burkitt lymphoma (BL). To date, there are no available drugs to target latent EBV, and the existing broad-spec trum antiviral drugs...