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Carbonic anhydrase inhibitors. Inhibition of cytosolic isoforms I, II, III, VII and XIII with less investigated inorganic anions
被引:33
|作者:
Innocenti, Alessio
[1
]
Scozzafava, Andrea
[1
]
Supuran, Claudiu T.
[1
]
机构:
[1] Univ Florence, Lab Chim Bioinorgan, I-50019 Florence, Italy
基金:
欧盟第七框架计划;
关键词:
Carbonic anhydrase;
Isoform I;
II;
III;
VIII;
XIII;
Inorganic anion;
Trithiocarbonate;
Zinc-binding group;
Dithiocarbamates;
ISOZYME-II;
X-RAY;
ANTITUMOR SULFONAMIDE;
SECRETORY ISOFORM;
CRYSTAL-STRUCTURE;
TRITHIOCARBONATES;
TRANSMEMBRANE;
SELECTIVITY;
THIOXOLONE;
AFFINITY;
D O I:
10.1016/j.bmcl.2009.02.088
中图分类号:
R914 [药物化学];
学科分类号:
100701 ;
摘要:
An inhibition study of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isoforms I, II, III, VII and XIII with anions such as stannate(IV), selenate(VI), tellurate(VI), perosmate(VIII), persulfate, pyrophosphate(V), pyrovanadate(V), tetraborate, persulfate, perrhenate(VII), perrutenate(VII), selenocyanate, iminodisulfonate,. fluorosulfate and trithiocarbonate is reported. Trithiocarbonate was the best inhibitor detected, showing affinities of 8.7-9.9 mu M for CA I-III, of 36.15 mM for CA VII and of 0.43 mM for CA XIII. Considering trithiocarbonate as lead, we show that compounds incorporating the new zinc-binding group CS2-, such as among other the dithiocarbamates, are even more active inhibitors, with submicromolar inhibitory activity. New classes of CA inhibitors are being detected based on the CS2- zinc-binding group. (C) 2009 Elsevier Ltd. All rights reserved.
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页码:1855 / 1857
页数:3
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