Search results for "Zole"
showing 10 items of 2482 documents
Anticancer properties of 5Z-(4- fuorobenzylidene)-2-(4- hydroxyphenylamino)-thiazol-4-one
2019
Abstract4-thiazolidinones, which are privileged structures in medicinal chemistry, comprise the well-known class of heterocycles and are a source of new drug-like compounds. Undoubtedly, the 5-bulky-substituted-2,4-thiazolidinediones - a class of antihyperglycemic glitazones, which are peroxisome proliferator-activated receptor gamma (PPARγ) agonists, are the most described group among them. As there are various chemically distinct 4-thiazolidinones, different subtypes have been selected for studies; however, their main pharmacological profiles are similar. The aim of this study was to evaluate the anticancer activity of 5Z-(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol-4-one (Les-2…
Strategies against nonsense: oxadiazoles as translational readthrough-inducing drugs (TRIDs)
2019
This review focuses on the use of oxadiazoles as translational readthrough-inducing drugs (TRIDs) to rescue the functional full-length protein expression in mendelian genetic diseases caused by nonsense mutations. These mutations in specific genes generate premature termination codons (PTCs) responsible for the translation of truncated proteins. After a brief introduction on nonsense mutations and their pathological effects, the features of various classes of TRIDs will be described discussing differences or similarities in their mechanisms of action. Strategies to correct the PTCs will be presented, particularly focusing on a new class of Ataluren-like oxadiazole derivatives in comparison …
Genotoxicity and Epigenotoxicity of Carbazole-Derived Molecules on MCF-7 Breast Cancer Cells
2021
The carbazole compounds PK9320 (1-(9-ethyl-7-(furan-2-yl)-9H-carbazol-3-yl)-N-methylmethanamine) and PK9323 (1-(9-ethyl-7-(thiazol-4-yl)-9H-carbazol-3-yl)-N-methylmethanamine), second-generation analogues of PK083 (1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine), restore p53 signaling in Y220C p53-mutated cancer cells by binding to a mutation-induced surface crevice and acting as molecular chaperones. In the present paper, these three molecules have been tested for mutant p53-independent genotoxic and epigenomic effects on wild-type p53 MCF-7 breast adenocarcinoma cells, employing a combination of Western blot for phospho-γH2AX histone, Comet assay and methylation-sensitive arbitrarily pr…
Treatment of multiple myeloma-related bone disease
2021
In this Policy Review, the Bone Working Group of the International Myeloma Working Group updates its clinical practice recommendations for the management of multiple myeloma-related bone disease. After assessing the available literature and grading recommendations using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method, experts from the working group recommend zoledronic acid as the preferred bone-targeted agent for patients with newly diagnosed multiple myeloma, with or without multiple myeloma-related bone disease. Once patients achieve a very good partial response or better, after receiving monthly zoledronic acid for at least 12 months, the treating…
Genetic inactivation of the sigma-1 chaperone protein results in decreased expression of the R2 subunit of the GABA-B receptor and increased suscepti…
2021
There is a growing body of evidence demonstrating the significant involvement of the sigma-1 chaperone protein in the modulation of seizures. Several sigma-1 receptor (Sig1R) ligands have been demonstrated to regulate the seizure threshold in acute and chronic seizure models. However, the mechanism by which Sig1R modulates the excitatory and inhibitory pathways in the brain has not been elucidated. The aim of this study was to compare the susceptibility to seizures of wild type (WT) and Sig1R knockout (Sig1R−/−) mice in intravenous pentylenetetrazol (PTZ) and (+)-bicuculline (BIC) infusion-induced acute seizure and Sig1R antagonist NE-100-induced seizure models. To determine pos…
Cost-effectiveness of buffered soluble alendronate 70 mg effervescent tablet for the treatment of postmenopausal women with osteoporosis in Italy
2021
Summary The use of buffered soluble alendronate 70 mg effervescent tablet, a convenient dosing regimen for bisphosphonate therapy, seems a cost-effective strategy compared with relevant alternative treatments for postmenopausal women with osteoporosis aged 60 years and over in Italy. Introduction To assess the cost-effectiveness of buffered soluble alendronate (ALN) 70 mg effervescent tablet compared with relevant alternative treatments for postmenopausal osteoporotic women in Italy. Methods A previously validated Markov microsimulation model was adjusted to the Italian healthcare setting to estimate the lifetime costs (expressed in €2019) per quality-adjusted life-years (QALY) of buffered …
CHK1-targeted therapy to deplete DNA replication-stressed, p53-deficient, hyperdiploid colorectal cancer stem cells.
2017
ObjectiveCancer stem cells (CSCs) are responsible for tumour formation and spreading, and their targeting is required for tumour eradication. There are limited therapeutic options for advanced colorectal cancer (CRC), particularly for tumours carrying RAS-activating mutations. The aim of this study was to identify novel CSC-targeting strategies.DesignTo discover potential therapeutics to be clinically investigated as single agent, we performed a screening with a panel of FDA-approved or investigational drugs on primary CRC cells enriched for CSCs (CRC-SCs) isolated from 27 patients. Candidate predictive biomarkers of efficacy were identified by integrating genomic, reverse-phase protein mic…
Ataluren for the Treatment of Usher Syndrome 2A Caused by Nonsense Mutations
2019
The identification of genetic defects that underlie inherited retinal diseases (IRDs) paves the way for the development of therapeutic strategies. Nonsense mutations caused approximately 12% of all IRD cases, resulting in a premature termination codon (PTC). Therefore, an approach that targets nonsense mutations could be a promising pharmacogenetic strategy for the treatment of IRDs. Small molecules (translational read-through inducing drugs
1-(Pyridin-4-yl)-3-(2,4,6-trichlorophenyl)benz[4,5]imidazo[1,2-d][1,2,4]triazin-4(3H)-one
2016
In the title compound, C20H10Cl3N5O, the 13-membered ring system makes dihedral angles of 78.64 (9)° with the trichlorophenyl ring and 62.60 (10)° with the pyridine ring. The crystal packing is dominated by π–π interactions between the 13-membered ring systems [centroid–centroid distance = 3.6655 (11)°].
Development of a method to determine axitinib, lapatinib and afatinib in plasma by micellar liquid chromatography and validation by the European Medi…
2017
A method based on micellar liquid chromatography to quantify the tyrosine kinase inhibitors axitinib, lapatinib and afatinib in plasma is reported. The sample pretreatment was a simple 1/5-dilution in a pure micellar solution, filtration and direct injection, without requiring extraction or purification steps. The three drugs were resolved from the matrix in 17 min, using an aqueous solution of 0.07 M sodium dodecyl sulfate – 6.0% 1-pentanol, buffered at pH 7 with 0.01 M phosphate salt as mobile phase, running under isocratic mode at 1 mL/min through a C18 column. The detection was performed by absorbance at 260 nm. An accurate mathematical relationship was established between the retention…