2 research outputs found
Influence of Surface Groups on Poly(propylene imine) Dendrimers Antiprion Activity
Prion diseases are characterized by the accumulation
of PrP<sup>Sc</sup>, an aberrantly folded isoform of the host protein
PrP<sup>C</sup>. Specific forms of synthetic molecules known as dendrimers
are able to eliminate protease-resistant PrP<sup>Sc</sup> in both
an intracellular and in vitro setting. The properties of a dendrimer
which govern this ability are unknown. We addressed the issue by comparing
the in vitro antiprion ability of numerous modified poly(propylene-imine)
dendrimers, which varied in size, structure, charge, and surface group
composition. Several of the modified dendrimers, including an anionic
glycodendrimer, reduced the level of protease resistant PrP<sup>Sc</sup> in a prion strain-dependent manner. This led to the formulation
of a new working model for dendrimer/prion interactions which proposes
dendrimers eliminate PrP<sup>Sc</sup> by destabilizing the protein
and rendering it susceptible to proteolysis. This ability is not dependent
on any particular charge of dendrimer, but does require a high density
of reactive surface groups
Oxaphosphinanes: New Therapeutic Perspectives for Glioblastoma
This paper reports the design and the synthesis of a
new family
of compounds, the phostines, belonging to the [1,2]oxaphosphinane
family. Twenty-six compounds have been screened for their antiproliferative
activity against a large panel of NCI cancer cell lines. Because of
its easy synthesis and low EC<sub>50</sub> value (500 nM against the
C6 rat glioma cell line), compound <b>3.1a</b> was selected
for further biological study. Moreover, the specific biological effect
of <b>3.1a</b> on the glioblastoma phylogenetic cluster from
the NCI is dependent on its stereochemistry. Within that cluster, <b>3.1a</b> has a higher antiproliferative activity than Temozolomide
and is more potent than paclitaxel for the SF295 and SNB75 cell lines.
In constrast with paclitaxel and vincristine, <b>3.1a</b> is
devoid of astrocyte toxicity. The original activity spectrum of <b>3.1a</b> on the NCI cancer cell line panel allows the development
of this family for use in association with existing drugs, opening
new therapeutic perspectives