Migotanie przedsionków - nowe leki, nowe nadzieje. Stan badań nad dronedaronem

Migotanie przedsionków jest najczęstszym rodzajem arytmii. Zwiększa ryzyko wystąpienia udaru niedokrwiennego mózgu i niewydolności serca oraz znacząco obniża jakość życia. Jak wykazano, spośród stosowanych w połączeniu z terapią przeciwkrzepliwą leków antyarytmicznych amiodaron jest najbardziej efektywny w prewencji napadów migotania przedsionków i podtrzymywaniu rytmu zatokowego. Jego stosowanie jest jednak znacznie ograniczone ze względu na działania niepożądane. Dronedaron to nowy lek pod względem strukturalnym zbliżony do amiodaronu, ale pozbawiony toksycznego wpływu, przede wszystkim na tarczycę i tkankę płucną. W dotychczas przeprowadzonych badaniach dowiódł swojej skuteczności w prewencji nawrotów migotania przedsionków. Jest również pierwszym lekiem antyarytmicznym, dla którego wykazano zmniejszenie częstości hospitalizacji z przyczyn sercowo-naczyniowych oraz zgonów i zmniejszenie częstości występowania udaru mózgu, a efekt ten wykraczał poza ochronne działanie stosowanej równocześnie terapii przeciwkrzepliwej. Niniejszy artykuł zawiera analizę dotychczas przeprowadzonych badań nad dronedaronem i rozważania, czy u części pacjentów można go stosować jako lek pierwszego rzutu. Choroby Serca i Naczyń 2010, 7 (2), 93-10

New phosphorus analogs of bevirimat: synthesis, evaluation of anti-HIV-1 activity and molecular docking study

Since the beginning of the human immunodeficiency virus (HIV) epidemic, many groups of drugs characterized by diverse mechanisms of action have been developed, which can suppress HIV viremia. 3-O-(3′,3′-Dimethylsuccinyl) betulinic acid, known as bevirimat (BVM), was the first compound in the class of HIV maturation inhibitors. In the present work, phosphate and phosphonate derivatives of 3-carboxyacylbetulinic acid were synthesized and evaluated for anti-HIV-1 activity. In vitro studies showed that 30-diethylphosphonate analog of BVM (compound 14a) has comparable effects to BVM (half maximal inhibitory concentrations (IC50) equal to 0.02 μM and 0.03 μM, respectively) and is also more selective (selectivity indices: 3450 and 967, respectively). To investigate the possible mechanism of antiviral effect of 14a, molecular docking was carried out on the C-terminal domain (CTD) of HIV-1 capsid (CA)–spacer peptide 1 (SP1) fragment of Gag protein, designated as CTD-SP1, which was described as a molecular target for maturation inhibitors. Compared with interactions between BVM and the protein, an increased number of strong interactions between ligand 14a and protein, generated by the phosphonate group, was observed

Phosphate Derivatives of 3-Carboxyacylbetulin: SynThesis, In Vitro Anti-HIV and Molecular Docking Study

Lupane-type pentacyclic triterpenes such as betulin and betulinic acid play an important role in the search for new therapies that would be effective in controlling viral infections. The aim of this study was the synthesis and evaluation of in vitro anti-HIV-1 activity for phosphate derivatives of 3-carboxyacylbetulin 3–5 as well as an in silico study of new compounds as potential ligands of the C-terminal domain of the HIV-1 capsid–spacer peptide 1 (CA-CTD-SP1) as a molecular target of HIV-1 maturation inhibitors. In vitro studies showed that 28-diethoxyphosphoryl-3-O-(3′,3′-dimethylsuccinyl)betulin (compound 3), the phosphate analog of bevirimat (betulinic acid derivative, HIV-1 maturation inhibitor), has IC50 (half maximal inhibitory concentration) equal to 0.02 μM. Compound 3 inhibits viral replication at a level comparable to bevirimat and is also more selective (selectivity indices = 1250 and 967, respectively). Molecular docking was used to examine the probable interaction between the phosphate derivatives of 3-carboxyacylbetulin and C-terminal domain (CTD) of the HIV-1 capsid (CA)–spacer peptide 1 (SP1) fragment of Gag protein, designated as CTD-SP1. Compared with interactions between bevirimat (BVM) and the protein, an increased number of strong interactions between ligand 3 and the protein, generated by the phosphate group, were observed. These compounds might have the potential to also inhibit SARS-CoV2 proteins, in as far as the intrinsically imprecise docking scores suggest

Ni–Cr Powders Modified with Rhenium as a Novel Coating Material—Physical Properties, Microstructure, and Behavior in Plasma Plume

The aim of this work was to develop a new coating material based on Ni20Cr alloy modified with up to 50%wt. rhenium. The modification was carried out by the mechanical mixing of the base powder and ammonium perrhenate with the subsequent thermoreduction in an H2 atmosphere. The obtained powder consists of a nickel–chromium core surrounded by a rhenium shell. The characterization of the powders—including their microstructure, phase and chemical composition, density, flowability, particle size distribution, and specific surface area—was performed. The influence of plasma current intensity and hydrogen gas flow on in-flight particle temperature and velocity were investigated. The results indicate that there is interdiffusion between the base Ni20Cr and the rhenium shell, resulting in intermediary solid solution(s). The modified powders have a higher specific surface area and a lower flowability, but this does not prevent them from being used as feedstock in plasma spraying. In-flight measurements reveal that increasing the content of rhenium allows for the higher temperature of particles, though it also reduces their speed