Search results for "Statin"

Venous Thrombosis Associated with HMG-CoA Reductase Inhibitors

2013

Abstract Among the various hypolipidemic drugs, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (also known as "statins") belong to a heterogeneous class of compounds, sharing an identical hypocholesterolemic effect that develops through direct inhibition of a rate-limiting step in endogenous cholesterol synthesis. Their mechanism of action entails competitive inhibition of HMG-CoA reductase. Several lines of evidence suggest that the pleiotropic effects of statins may also play a role in prevention of venous thrombosis, wherein hypercholesterolemic patients are characterized by enhanced thrombin generation, increased susceptibility to endothelial dysfunction and plate…

Synthesis and biological evaluation of cyclic derivatives of combretastatin A-4 containing group 14 elements

2018

Several tricyclic compounds inspired by the structure of combretastatin A-4 and bearing group 14 elements have been synthesized by homocoupling lithiated aryl fragments followed by ring-closing metathesis. These tricyclic compounds and their diolefin precursors were evaluated for their antiproliferative action on the tumor cell lines HT-29, MCF-7, HeLa and A-549 and on the non-tumor cell line HEK-293. In addition, their effects on the cell cycle were also measured. The tricyclic compounds show antiproliferative activity similar to that of combretastatin A-4, even though they are not so active in arresting the cell cycle. However, some diolefin precursors are able to cause accumulation of ce…

Six-Membered Rings, and Their Fused Derivatives

2015

Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-N,N-dimethylamino benzo[b]furan derivatives as inhibitors of tubulin polymeri…

2008

Molecules that target microtubules have an important role in the treatment of cancer. A new class of inhibitors of tubulin polymerization based on the 2-(3,4,5-trimethoxybenzoyl)-2-dimethylamino-benzo[b]furan molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-(3,4,5-trimethoxybenzoyl)-3-dimethylamino-6-methoxy-benzo[b]furan, which inhibits cancer cell growth at nanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.

Gold(I) Biscarbene Complexes Derived from Vascular-Disrupting Combretastatin A-4 Address Different Targets and Show Antimetastatic Potential

2014

Gold N-heterocyclic carbene (NHC) complexes are an emerging class of anticancer drugs. We present a series of gold(I) biscarbene complexes with NHC ligands derived from the plant metabolite combretastatin A-4 (CA-4) that retain its vascular-disrupting effect, yet address different cellular and protein targets. Unlike CA-4, these complexes did not interfere with tubulin, but with the actin cytoskeleton of endothelial and cancer cells. For the highly metastatic 518A2 melanoma cell line this effect was accompanied by a marked accumulation of cells in the G1 phase of the cell cycle and a suppression of active prometastatic matrix metalloproteinase-2. Despite these mechanistic differences the co…

Lipid-Altering Efficacy of Ezetimibe/Simvastatin 10/20 mg Compared to Rosuvastatin 10 mg in High-Risk Patients with and without Type 2 Diabetes Melli…

2010

AIMS: This post hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg (EZE/SIMVA) or rosuvastatin 10 mg (ROSUVA) in uncontrolled high-risk hypercholesterolemic patients with/without type 2 diabetes mellitus (T2DM) despite statin monotherapy. METHODS: Patients (n = 618) at high risk for coronary vascular disease with elevated LDL-C ≥100 and ≤190 mg/dL despite use of statins were randomized 1:1 to double-blind EZE/SIMVA 10/20 mg or ROSUVA 10 mg for 6 weeks. Patients were classified as having T2DM based on ≥1 of the following: diagnosis of T2DM, antidiabetic medication, or FPG ≥126 mg/dL. This analysis evaluated percent changes from baseline in lipids among patients …

Phenotypical and Functional Alteration of γδ T Lymphocytes in COVID-19 Patients: Reversal by Statins

2022

(1) Background: statins have been considered an attractive class of drugs in the pharmacological setting of COVID-19 due to their pleiotropic properties and their use correlates with decreased mortality in hospitalized COVID-19 patients. Furthermore, it is well known that statins, which block the mevalonate pathway, affect γδ T lymphocyte activation. As γδ T cells participate in the inflammatory process of COVID-19, we have investigated the therapeutical potential of statins as a tool to inhibit γδ T cell pro-inflammatory activities; (2) Methods: we harvested peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild clinical manifestatio…

Alteration of DNA topoisomerase II activity during infection of H9 cells by human immunodeficiency virus type 1 in vitro: a target for potential ther…

1990

Infection of H9 cells with human immunodeficiency virus type 1 (HIV-1) was found to decrease the phosphorylation of DNA topoisomerase II during the initial phase of infection. Simultaneously, with a later overshoot of phosphorylation and the subsequent activation of DNA topoisomerase II, the production of HIV-1 started. Applying three new protein kinase C inhibitors from the class of O-alkylglycerophospholipids we demonstrated that inhibition of protein kinase C-mediated phosphorylation of DNA topoisomerase II resulted in an inhibition of HIV-1 production. Based on the differential effect of the two protein kinase C activators, phorbol ester and bryostatin, we conclude that phosphorylation …

Myostatin and related proteins on the control of skeletal muscle mass and capillary density

2013

Skeletal muscle wasting is a feature of many pathological conditions such as muscular dystrophies, cancer and diabetes. Human ageing also results in the progressive loss of muscle mass and strength, a condition known as sarcopenia (or myopenia). Therefore, interventions that can reverse or slow down muscle loss are highly desirable. The TGF-β member myostatin is a well-known inhibitor of skeletal muscle growth, but it may also, if deleted, decrease muscle oxidative capacity. We have used the activin receptor 2B (ActR2B) fused to the Fc region of immunoglobulin G (ActR2B-Fc) as a trap to sequester myostatin and inhibit its activity. We sought to evaluate possible differences between doses an…

Inhibitory influence of chromogranin A N-terminal fragment (vasostatin-1) on the spontaneous contractions of rat proximal colon

2005

Very little is known about the role played by CGA and its fragments in the gastrointestinal physiology. We have studied the role of CGA N-terminal fragments in the regulation of intestinal smooth muscle contractility by measuring the influence of recombinant CGA 1-78 (VS-1) and synthetic CGA 7-57 peptides on the spontaneous mechanical activity of rat proximal colon in vitro. The mechanical activity was recorded as changes in the intraluminal pressure. VS-1 (0.1-30 nM) and CGA 7-57 (10-300 nM) produced concentration-dependent inhibitory effects, characterized by a progressive decrease in the mean amplitude of circular muscle spontaneous contractions, without affecting the resting tone. The r…