5 research outputs found
Structural formulae of Artemisinin and synthetic derivatives belonging to the first category AJ.
<p>Structural formulae of Artemisinin and synthetic derivatives belonging to the first category AJ.</p
<i>In vitro</i> anti-HCV activity of Artemisinin and its selected analogues on the replication of infectious HCVcc as measured by means of qRT-PCR (n = 4).
<p>a) ART; b) TVN4; c) AJ-002 and d) AJ-004. Bars indicate the HCV RNA level as compared to control (%) and lines represent the cell growth as compared to untreated controls (%).</p
Structural formulae of Artemisinin and synthetic derivatives belonging to the second category TVN.
<p>Structural formulae of Artemisinin and synthetic derivatives belonging to the second category TVN.</p
Effect of ART and derivatives on Huh 5-2 HCV replicon replication.
<p>∶ 50% effective concentration, CC50∶ 50% cytostatic concentration. Data obtained from the measurement of the firefly luciferase activity, and are mean values ± SD for four independent experiments (expressed in µM).<sup></sup> EC50</p><p>µM, Hemin inhibits HCV replicon replication by 30%.<sup></sup> Values between brackets indicate fold-change. At 5 </p
Design, Synthesis, and Biological Evaluation of Novel, Highly Active Soft ROCK Inhibitors
ROCK1
and ROCK2 play important roles in numerous cellular functions,
including smooth muscle cell contraction, cell proliferation, adhesion,
and migration. Consequently, ROCK inhibitors are of interest for treating
multiple indications including cardiovascular diseases, inflammatory
and autoimmune diseases, lung diseases, and eye diseases. However,
systemic inhibition of ROCK is expected to result in significant side
effects. Strategies allowing reduced systemic exposure are therefore
of interest. In a continuing effort toward identification of ROCK
inhibitors, we here report the design, synthesis, and evaluation of
novel soft ROCK inhibitors displaying an ester function allowing their
rapid inactivation in the systemic circulation. Those compounds display
subnanomolar activity against ROCK and strong differences of functional
activity between parent compounds and expected metabolites. The binding
mode of a representative compound was determined experimentally in
a single-crystal X-ray diffraction study. Enzymes responsible for
inactivation of these compounds once they enter systemic circulation
are also discussed