Ironjustic
Mon, Mar-06-06, 17:16
Anticancer Drug Des. 2001 Aug-Oct;16(4-5):195-207. Related
Articles, Links
The desferrithiocin (DFT) class of iron chelators: potential
as antineoplastic agents.
Kicic A, Chua AC, Baker E.
Department of Physiology, University of Western Australia,
Nedlands, Australia.
Iron (Fe) is essential for the proliferation of cancer cells.
A subgroup of the orthosubstituted phenolate class of Fe
chelators, desferrithiocin [2-(3'-hydroxypyrid-2'-yl)4-methyl-
-delta2-thiazoline-4(S)-carboxylic acid; DFT] and its
analogues, have potential application in short-term
chemotherapy for cancer by Fe deprivation. Their effects on
cell proliferation, cell cycle progression, Fe uptake and
toxicity were therefore examined in adult and fetal rat and
human hepatocellular carcinoma (HCC) cell lines, as well as in
normal cells. DFT was more active than desferrioxamine, in
clinical trials as an antineoplastic agent, consistently
inhibiting cell proliferation in all cell lines (IC50 = 40
microM).
2-(2'-hydroxyphenyl-2'-yl)-delta2-thiazoline-4(S)-carboxylic
acid was the most active analogue (IC50 = 55-90 microM).
Inhibition was affected by chelator concentration and ability
to prevent Fe uptake. The fetal-cell-derived HCC was more
susceptible than adult HCC. Structure-activity studies
revealed that thiazol methyl deletion greatly diminished
antiproliferative activity of the chelators but stereochemical
orientation of COOH around C4 had no effect. Removal of the N
from the pyridine ring restored antiproliferative activity.
Chelators inhibited DNA synthesis in the S phase. The
chelators at their IC50 concentration had little or no effect
on Fe uptake in normal cells. This apparent selectivity of
these chelators for cancer cells, coupled with their high
activity, suggests that further investigation is warranted.
PMID: 12049478 [PubMed - indexed for MEDLINE]
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Articles, Links
The desferrithiocin (DFT) class of iron chelators: potential
as antineoplastic agents.
Kicic A, Chua AC, Baker E.
Department of Physiology, University of Western Australia,
Nedlands, Australia.
Iron (Fe) is essential for the proliferation of cancer cells.
A subgroup of the orthosubstituted phenolate class of Fe
chelators, desferrithiocin [2-(3'-hydroxypyrid-2'-yl)4-methyl-
-delta2-thiazoline-4(S)-carboxylic acid; DFT] and its
analogues, have potential application in short-term
chemotherapy for cancer by Fe deprivation. Their effects on
cell proliferation, cell cycle progression, Fe uptake and
toxicity were therefore examined in adult and fetal rat and
human hepatocellular carcinoma (HCC) cell lines, as well as in
normal cells. DFT was more active than desferrioxamine, in
clinical trials as an antineoplastic agent, consistently
inhibiting cell proliferation in all cell lines (IC50 = 40
microM).
2-(2'-hydroxyphenyl-2'-yl)-delta2-thiazoline-4(S)-carboxylic
acid was the most active analogue (IC50 = 55-90 microM).
Inhibition was affected by chelator concentration and ability
to prevent Fe uptake. The fetal-cell-derived HCC was more
susceptible than adult HCC. Structure-activity studies
revealed that thiazol methyl deletion greatly diminished
antiproliferative activity of the chelators but stereochemical
orientation of COOH around C4 had no effect. Removal of the N
from the pyridine ring restored antiproliferative activity.
Chelators inhibited DNA synthesis in the S phase. The
chelators at their IC50 concentration had little or no effect
on Fe uptake in normal cells. This apparent selectivity of
these chelators for cancer cells, coupled with their high
activity, suggests that further investigation is warranted.
PMID: 12049478 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
-------------------
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking