Innocenti Alessio, Scozzafava Andrea, Supuran Claudiu T
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
Bioorg Med Chem Lett. 2009 Apr 1;19(7):1855-7. doi: 10.1016/j.bmcl.2009.02.088. Epub 2009 Feb 26.
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 microM 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.
报道了对胞质碳酸酐酶(CA,EC 4.2.1.1)同工型I、II、III、VII和XIII与锡酸盐(IV)、硒酸盐(VI)、碲酸盐(VI)、高锇酸盐(VIII)、过硫酸盐、焦磷酸盐(V)、焦钒酸盐(V)、四硼酸盐、过硫酸盐、高铼酸盐(VII)、高钌酸盐(VII)、硒氰酸盐、亚氨基二磺酸盐、氟硫酸盐和三硫代碳酸盐等阴离子的抑制研究。三硫代碳酸盐是检测到的最佳抑制剂,对CA I - III的亲和力为8.7 - 9.9 microM,对CA VII为36.15 mM,对CA XIII为0.43 mM。以三硫代碳酸盐为先导,我们发现含有新的锌结合基团CS2-的化合物,如二硫代氨基甲酸盐等,是活性更高的抑制剂,具有亚微摩尔级的抑制活性。基于CS2-锌结合基团正在检测新型的CA抑制剂。