8 research outputs found
Solvent-Free Synthesis of α‑Amino Nitrile-Derived Ureas
An efficient and environmentally friendly methodology for the solvent-free synthesis of α-amino nitrile derived ureas from α-amino acid based amino nitriles has been developed. At room temperature no epimerization was observed in the resulting ureas, but under microwave heating, epimerization occurred at the chiral center bearing the cyano group
Azepane Quaternary Amino Acids As Effective Inducers of 3<sub>10</sub> Helix Conformations
A simple method for the synthesis of an azepane quaternary
amino
acid in enantiopure form is described. Theoretical, NMR, and X-ray
studies indicated that this azepane-derived amino acid is an effective
stabilizer of 3<sub>10</sub> helical structures in short peptides
Azepane Quaternary Amino Acids As Effective Inducers of 3<sub>10</sub> Helix Conformations
A simple method for the synthesis of an azepane quaternary
amino
acid in enantiopure form is described. Theoretical, NMR, and X-ray
studies indicated that this azepane-derived amino acid is an effective
stabilizer of 3<sub>10</sub> helical structures in short peptides
ITH14001, a CGP37157-Nimodipine Hybrid Designed to Regulate Calcium Homeostasis and Oxidative Stress, Exerts Neuroprotection in Cerebral Ischemia
During
brain ischemia, oxygen and glucose deprivation induces calcium
overload, extensive oxidative stress, neuroinflammation, and, finally,
massive neuronal loss. In the search of a neuroprotective compound
to mitigate this neuronal loss, we have designed and synthesized a
new multitarget hybrid (ITH14001) directed at the reduction of calcium
overload by acting on two regulators of calcium homeostasis; the mitochondrial
Na<sup>+</sup>/Ca<sup>2+</sup> exchanger (mNCX) and L-type voltage
dependent calcium channels (VDCCs). This compound is a hybrid of CGP37157
(mNCX inhibitor) and nimodipine (L-type VDCCs blocker), and its pharmacological
evaluation revealed a moderate ability to selectively inhibit both
targets. These activities conferred concentration-dependent neuroprotection
in two models of Ca<sup>2+</sup> overload, such as toxicity induced
by high K<sup>+</sup> in the SH-SY5Y cell line (60% protection at
30 μM) and veratridine in hippocampal slices (26% protection
at 10 μM). It also showed neuroprotective effect against oxidative
stress, an activity related to its nitrogen radical scavenger effect
and moderate induction of the Nrf2-ARE pathway. Its Nrf2 induction
capability was confirmed by the increase of the expression of the
antioxidant and anti-inflammatory enzyme heme-oxygenase I (3-fold
increase). In addition, the multitarget profile of ITH14001 led to
anti-inflammatory properties, shown by the reduction of nitrites production
induced by lipopolysaccharide in glial cultures. Finally, it showed
protective effect in two acute models of cerebral ischemia in hippocampal
slices, excitotoxicity induced by glutamate (31% protection at 10
μM) and oxygen and glucose deprivation (76% protection at 10
μM), reducing oxidative stress and iNOS deleterious induction.
In conclusion, our hybrid derivative showed improved neuroprotective
properties when compared to its parent compounds CGP37157 and nimodipine
FormylBODIPYs: Privileged Building Blocks for Multicomponent Reactions. The Case of the Passerini Reaction
Eleven
formyl-containing BODIPY dyes were prepared by means of either the
Liebeskind–Srogl cross-coupling reaction or the Vilsmeier reaction.
These dyes were used as components in the Passerini reaction to give
highly substituted BODIPY dyes. A joined spectroscopic and theoretical
characterization of the synthesized compounds was conducted to unravel
the impact of the structural rigidity/flexibility on the photophysical
signatures. These dyes were tested as fluorescent trackers for phagocytosis.
Additionally, they proved to be useful to stain different blood cells
with an intense and stable signal at a very low exposure time