Substituent effects on desferrithiocin and desferrithiocin analogue iron-clearing and toxicity profiles.
Substituent effects on desferrithiocin and desferrithiocin analogue iron-clearing and toxicity profiles.
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DOI：
10.1021/jm300509y
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发表时间：
2012-08-23
影响因子：
7.3
通讯作者：
McManis, James S.
中科院分区：
文献类型：
--
作者：
Bergeron, Raymond J.;Wiegand, Jan;Bharti, Neelam;McManis, James S.
Desferrithiocin (DFT, 1) is a very efficient iron chelator when given orally. However, it is severely nephrotoxic. Structure-activity studies with 1 demonstrated that removal of the aromatic nitrogen to provide desazadesferrithiocin (DADFT, 2) and introduction of either a hydroxyl group or a polyether fragment onto the aromatic ring resulted in orally active iron chelators that were much less toxic than 1. The purpose of the current study was to determine if a comparable reduction in renal toxicity could be achieved by performing the same structural manipulations on 1 itself. Accordingly, three DFT analogues were synthesized. Iron clearing efficiency and ferrokinetics were evaluated in rats and primates; toxicity assessments were carried out in rodents. The resulting DFT ligands demonstrated a reduction in toxicity that was equivalent to that of the DADFT analogues and presented with excellent iron clearing properties.
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影响因子：
7.3
作者：
Bergeron, Raymond J.;Wiegand, Jan;Singh, Shailendra
通讯作者：
Singh, Shailendra
影响因子：
20.3
作者：
Bergeron, RJ;Wiegand, J;Brittenham, GM
通讯作者：
Brittenham, GM
影响因子：
2
作者：
Bergeron, RJ;Wiegand, J;Abboud, KA
通讯作者：
Abboud, KA
影响因子：
4.4
作者：
Dunaief, Joshua L.
通讯作者：
Dunaief, Joshua L.
DOI：
10.1039/c39900001194
发表时间：
1990-09-01
影响因子：
--
作者：
ANDEREGG, G;RABER, M
通讯作者：
RABER, M