2 research outputs found
Stable 5,5ā²-Substituted 2,2ā²-Bipyrroles: Building Blocks for Macrocyclic and Materials Chemistry
The preparation and
characterization of a family of stable 2,2ā²-bipyrroles
substituted at positions 5 and 5ā² with thienyl, phenyl, TMS-ethynyl,
and vinyl groups is reported herein. The synthesis of these new bipyrroles
comprises three steps: formation of the corresponding 5,5ā²-unsubstituted
bipyrrole, bromination, and Stille or Suzuki coupling. The best results
in the coupling are obtained using the Stille reaction under microwave
irradiation. The new compounds have been fully characterized by UVāvis
absorption, fluorescence, and IR spectroscopies and cyclic voltammetry.
X-ray single-crystal analysis of four of the synthesized bipyrroles
indicates a trans coplanar geometry of the pyrrole rings. Furthermore,
the substituents at positions 5,5ā² remain coplanar to the central
rings. This particular geometry extends the Ļ-conjugation of
the systems, which is in agreement with a red-shifting observed for
the Ī»<sub>max</sub> of the substituted molecules compared to
the unsubstituted bipyrrole. All of these new compounds display a
moderate fluorescence. In contrast with unsubstituted bipyrroles,
these bipyrroles are endowed with a high chemical and thermal stability
and solubility in organic solvents
Noncyclam Tetraamines Inhibit CXC Chemokine Receptor Type 4 and Target Glioma-Initiating Cells
The three stereoisomers of the noncyclam compound <b>1</b> (<b>1</b>(<i>R,R</i>), <b>1</b>(<i>S,S</i>), and the <i>meso</i> form <b>1</b>(<i>S,R</i>)) and their corresponding tetrahydrochlorides <b>11</b> were
prepared from (<i>S</i>)- and (<i>R</i>)-2-methylpiperidine.
We have evaluated their inhibitory activity on the CXC chemokine receptor
type 4 (CXCR4), toxicity properties, and assessment of their effect
on glioma initiating cells (GICs) in comparison with the prototype
compound AMD3100. The IC<sub>50</sub> values determined on human recombinant
(CHO) cells showed very similar inhibitory activities albeit a lower <i>K</i><sub>B</sub> for AMD3100, with the <b>1</b>(<i>R,R</i>) isomer being second in potency. All the compounds showed
low cardiac toxicity but, contrary to AMD3100, gave maximum nonlethal
doses of around 2.0 mg/kg. The CXCR4 inhibitors had an effect on the
state of differentiation of GICs, decreasing the percentage of CD44+
cells in glioblastoma multiform neurospheres in vitro. Moreover, these
CXCR4 inhibitors blocked the capacity of cells to initiate orthotopic
tumors in immunocompromised mice