ironjustice
2012-08-11 00:07:01 UTC
Polyaminoquinoline Iron Chelators for Vectorization of
Antiproliferative Agents: Design, Synthesis and Validation.
Bioconjug Chem. 2012 Aug 8.
Deniaud D, Corcé V, Morin E, Guihéneuf S, Renault E, Renaud S, Cannie
I, Tripier R, Lima L, Julienne K, Gouin SG, Loreal O, Gaboriau F.
Abstract
Iron chelation in tumoral cells has been reported as potentially
useful during antitumoral treatment.
Our aim was to develop new polyaminoquinoline iron chelators targeting
tumoral cells.
For this purpose, we designed, synthesized and evaluated the
biological activity of a new generation of iron chelators, which we
named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold
linked to linear polyamine vectors.
These were designed to target tumor cells expressing an overactive
polyamine transport system (PTS).
A set of Quilamines bearing variable polyamine chains was designed and
assessed for their ability to interact with iron.
Quilamines were also screened for their cytostatic/cytotoxic effects
and their selective uptake by the PTS in the CHO cell line. Our
results show that both the 8-HQ moiety and the polyamine part
participate in the iron coordination. HQ1-44, the most promising
Quilamine identified, presents a homospermidine moiety and was shown
to be highly taken up by the PTS and to display an efficient
antiproliferative activity that occurred in the micromolar range.
In addition, cytotoxicity was only observed at concentrations higher
than 100 µM.
We also demonstrated the high complexation capacity of HQ1-44 with
iron while much weaker complexes were formed with other cations,
indicative of a high selectivity.
We applied the density functional theory to study the binding energy
and the electronic structure of prototypical iron(III)-Quilamine
complexes. On the basis of these calculations, Quilamine HQ1-44 is a
strong tridentate ligand for iron(III) especially in the form of a 1:2
complex.
PMID:22873526
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Tom
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Antiproliferative Agents: Design, Synthesis and Validation.
Bioconjug Chem. 2012 Aug 8.
Deniaud D, Corcé V, Morin E, Guihéneuf S, Renault E, Renaud S, Cannie
I, Tripier R, Lima L, Julienne K, Gouin SG, Loreal O, Gaboriau F.
Abstract
Iron chelation in tumoral cells has been reported as potentially
useful during antitumoral treatment.
Our aim was to develop new polyaminoquinoline iron chelators targeting
tumoral cells.
For this purpose, we designed, synthesized and evaluated the
biological activity of a new generation of iron chelators, which we
named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold
linked to linear polyamine vectors.
These were designed to target tumor cells expressing an overactive
polyamine transport system (PTS).
A set of Quilamines bearing variable polyamine chains was designed and
assessed for their ability to interact with iron.
Quilamines were also screened for their cytostatic/cytotoxic effects
and their selective uptake by the PTS in the CHO cell line. Our
results show that both the 8-HQ moiety and the polyamine part
participate in the iron coordination. HQ1-44, the most promising
Quilamine identified, presents a homospermidine moiety and was shown
to be highly taken up by the PTS and to display an efficient
antiproliferative activity that occurred in the micromolar range.
In addition, cytotoxicity was only observed at concentrations higher
than 100 µM.
We also demonstrated the high complexation capacity of HQ1-44 with
iron while much weaker complexes were formed with other cations,
indicative of a high selectivity.
We applied the density functional theory to study the binding energy
and the electronic structure of prototypical iron(III)-Quilamine
complexes. On the basis of these calculations, Quilamine HQ1-44 is a
strong tridentate ligand for iron(III) especially in the form of a 1:2
complex.
PMID:22873526
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/634q5a
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk