The 3-hydroxy-3-methylglutaryl neohesperidosides of hesperetin (brutieridin, 1) and naringenin (melitidin, 2) were isolated and detected from the fruits of bergamot (Citrus bergamia). The structures of these compounds were determined by spectroscopic and chemical methods.
Imaging
mass spectrometry (IMS) was employed for the analysis of
frozen skin biopsies to investigate the differences between stage
IV pressure ulcers that remain stalled, stagnant, and unhealed versus
those exhibiting clinical and histological signs of improvement. Our
data reveal a rich diversity of proteins that are dynamically modulated,
and we selectively highlight a family of calcium binding proteins
(S-100 molecules) including calcyclin (S100-A6), calgranulins A (S100-A8)
and B (S100-A9), and calgizzarin (S100-A11). IMS allowed us to target
three discrete regions of interest: the wound bed, adjacent dermis,
and hypertrophic epidermis. Plots derived using unsupervised principal
component analysis of the global protein signatures within these three
spatial niches indicate that these data from wound signatures have
potential as a prognostic tool since they appear to delineate wounds
that are favorably responding to therapeutic interventions versus
those that remain stagnant or intractable in their healing status.
Our discovery-based approach with IMS augments current knowledge of
the molecular signatures within pressure ulcers while providing a
rationale for a focused examination of the role of calcium modulators
within the context of impaired wound healing.
A small library of psoralen carboxylic acids and their corresponding benzenesulfonamide derivatives were designed and synthesized to evaluate their activity and selectivity toward tumor associated human carbonic anhydrase (hCA) isoforms IX and XII. Both psoralen acids and sulfonamides exhibited potent inhibition of IX and XII isozymes in the nanomolar concentration range. However, psoralen acids resulted as the most selective in comparison with the corresponding benzenesulfonamide derivatives. Our data indicate that the psoralen scaffold is a promising starting point for the design of highly selective tumor associated hCA inhibitors.
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