The
bark of trees contains an interesting mixture of bioactive
compounds, or so-called extractives. The use of supercritical carbon
dioxide (sc-CO2) eliminates both the need for organic solvents
as extractants and the danger that solvent traces might compromise
the purity of the extracts. Unfortunately, the complexity and natural
variability of extracts’ composition render any utilization
attempts rather challenging. Thus, in order to implement exploitation
concepts in a meaningful way, appropriate analytical techniques for
characterizing extracts must be available beforehand. In our work,
we explored gas chromatography coupled to both mass spectrometry and
a flame ionization detector (GC-MS/FID), in combination with ultraperformance
convergence chromatography and quadrupole time-of-flight mass spectrometry
(UPC2-QTof-MS), for the characterization of bark extracts
from pine (Pinus sylvestris L.) in both qualitative
and quantitative terms. Although the conventional GC-MS/FID approach
is a robust method for overall quantification of extractives, it fails
to provide ample information about native sterol esters and triglycerides.
These data are provided by a new, complementary analytical technique
based on supercritical carbon dioxide, as the chromatographic eluant,
coupled to a high-resolution mass spectrometer. The combination of
both techniques and the use of sc-CO2 as both an extraction
solvent and eluant made this combined tool especially powerful. The
most prominent triglycerides in the extract were identified qualitatively
and quantitatively, and the dominating sterol esters were identified
qualitatively, by UPC2-QTof-MS.
Acid-sensitive ion channels (ASICs) are sodium channels partially permeable to Ca 2+ ions, listed among putative targets in central nervous system (CNS) diseases in which a pH modification occurs. We targeted novel compounds able to modulate ASIC1 and to reduce the progression of ischemic brain injury. We rationally designed and synthesized several diminazeneinspired diaryl mono-and bis-guanyl hydrazones. A correlation between their predicted docking affinities for the acidic pocket (AcP site) in chicken ASIC1 and their inhibition of homo-and heteromeric hASIC1 channels in HEK-293 cells was found. Their activity on murine ASIC1a currents and their selectivity vs mASIC2a were assessed in engineered CHO-K1 cells, highlighting a limited isoform selectivity. Neuroprotective effects were confirmed in vitro, on primary rat cortical neurons exposed to oxygen-glucose deprivation followed by reoxygenation, and in vivo, in ischemic mice. Early lead 3b, showing a good selectivity for hASIC1 in human neurons, was neuroprotective against focal ischemia induced in mice.
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