Search results for "Drugs"
showing 10 items of 747 documents
Integrating theoretical and experimental permeability estimations for provisional biopharmaceutical classification: Application to the WHO essential …
2018
The accuracy of the provisional estimation of the Biopharmaceutics Classification System (BCS) is heavily influenced by the permeability measurement. In this study, several theoretical and experimental models currently employed for BCS permeability classification have been analysed. The experimental models included the in situ rat intestinal perfusion, the ex vivo rat intestinal tissue in an Ussing chamber, the MDCK and Caco-2 cell monolayers, and the parallel artificial membrane (PAMPA). The theoretical models included the octanol-water partition coefficient and the QSPeR (Quantitative Structure-Permeability Relationship) model recently developed. For model validation, a dataset of 43 comp…
Chemical profiling of the synthetic cannabinoid MDMB-CHMICA: Identification, assessment, and stability study of synthesis-related impurities in seize…
2019
In this work, the most discriminating synthesis-related impurities found in samples from seizures and controlled synthesis of the synthetic cannabinoid MDMB-CHMICA (methyl (S)-2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate) were characterized. Based on 61 available powder samples of MDMB-CHMICA, 15 key-impurities were assessed, isolated in larger quantities via flash chromatography and structurally elucidated and characterized via high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Apart from verifying the relation of the impurities to the major component, the interpretation of their chemical structures with distinct structural elements pro…
Molecular modeling approaches in the discovery of new drugs for anti-cancer therapy: the investigation of p53-MDM2 interaction and its inhibition by …
2010
The mdm2 oncogene product, MDM2, is an ubiquitin protein ligase that inhibits the transcriptional activity of the tumor suppressor p53 and promotes its degradation. About 50% of all human cancers present mutations or deletions in the TP53 gene. In the remaining half of all human neoplasias that express the wild-type protein, aberrations of p53 regula- tors, such as MDM2, account for p53 inhibition. For this reason, designing small-molecule inhibitors of the p53-MDM2 protein-protein interaction is a promising strategy for the treatment of cancers retaining wild-type p53. The development of inhibitors has been challenging. Although many small-molecule MDM2 inhibitors have shown potent in vitr…
Similarity-Based Virtual Screening to Find Antituberculosis Agents Based on Novel Scaffolds: Design, Syntheses and Pharmacological Assays
2022
A method to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC) is developed. A set of structurally heterogeneous agents against MTBC was used to obtain a mathematical model based on topological descriptors. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets. It was also useful to select new potential antituberculosis compounds in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5-a]pyrimidines was particularly interesting because these structures could provide new scaffolds in this field. T…
Estimation of Solute-Stationary Phase and Solute-Mobile Phase Interactions in the Presence of Ionic Liquids
2019
The presence of free silanols on alkyl-bonded reversed-phase stationary phases is responsible for broad and asymmetrical peaks when basic drugs are chromatographed with conventional octadecylsilane (C18) columns due to ionic interactions. In the last few years, ionic liquids (ILs) have attracted attention to reduce this undesirable silanol activity. ILs should be considered as dual modifiers (with a cationic and anionic character), which means that both cations and anions are able to adsorb on the stationary phase, creating a positively or negatively charged layer, depending on the relative adsorption. The accessibility of basic compounds to the silanols is prevented by both the IL cation a…
Increased recovery of brain acetylcholinesterase activity in dichlorvos-intoxicated European eels Anguilla anguilla by bath treatment with N-acetylcy…
2003
Organophosphate (OP) pesticides are widely used as antiparasitic chemicals in finfish aquaculture. However, current antidotes cannot be applied to treat intoxicated fish. We showed in previous studies the importance of glutathione (GSH) metabolism in pesticide resistance of the European eel Anguilla anguilla L. The present work studied the effects of the antioxidant and glutathione pro-drug N-acetyl-l-cysteine (NAC) on the recovery of European eels exposed for 96 h to a sublethal concentration (0.17 mg l^-1; 20% of its 96 h LC50) of the OP pesticide dichlorvos (2,2-dichlorovinyl dimethyl phosphate; DDVP). This insecticide and acaricide decreased muscular GSH content and increased oxidised g…
Tonographic Effect of Ocular Response Analyzer in Comparison to Goldmann Applanation Tonometry.
2016
AIMS The tonographic effect is a phenomenon of intraocular pressure (IOP) reduction following repeated tonometry. This study examines whether the tonographic effect occurs following IOP measurement performed with Ocular Response Analyzer (ORA). METHODS Both eyes of 31 glaucoma patients and 35 healthy controls underwent nine IOP-measurements performed with GAT and ORA. The number of GAT and ORA measurements performed on each eye differed depending on the randomly allocated investigation scheme. Central corneal thickness (CCT), anterior chamber volume (ACV) and anterior chamber depth (ACD) were assessed with Pentacam before and after the repeated GAT/ORA measurements. RESULTS There was no sta…
Medium-term Culture of Normal Human Oral Mucosa: A Novel Three-dimensional Model to Study the Effectiveness of Drugs Administration
2012
Tissue-engineered oral mucosal equivalents have been developed for in vitro studies for a few years now. However, the usefulness of currently available models is still limited by many factors, mainly the lack of a physiological extracellular matrix (ECM) and the use of cell populations that do not reflect the properly differentiated cytotypes of the mucosa of the oral cavity. For this reason, we have developed a novel three-dimensional culture model reflecting the normal architecture of the human oral mucosa, with the main aim of creating a better in vitro model where to test cellular responses to drugs administration. This novel 3D cell culture model (3D outgrowth) was set up using an arti…
Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma
2021
The invasive tumor front (the tumor–host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. Herein we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression, and epigenetic profiles of classified aggressive primary uterine adenocarcinomas (24 patients) and leiomyosarcomas (11 patients). Sections of formalin-fixed samples before and after microdissection were scanned and studied. Reticular fiber archit…
The Peptide Hemopressin Acts through CB1Cannabinoid Receptors to Reduce Food Intake in Rats and Mice
2010
Hemopressin is a short, nine amino acid peptide (H-Pro-Val-Asn-Phe-Lys-Leu-Leu-Ser-His-OH) isolated from rat brain that behaves as an inverse agonist at the cannabinoid receptor CB1, and is shown here to inhibit agonist-induced receptor internalization in a heterologous cell model. Since this peptide occurs naturally in the rodent brain, we determined its effect on appetite, an established central target of cannabinoid signaling. Hemopressin dose-dependently decreases night-time food intake in normal male rats and mice, as well as in obeseob/obmale mice, when administered centrally or systemically, without causing any obvious adverse side effects. The normal, behavioral satiety sequence is …