Carbonic anhydrase inhibitors: Inhibition of the tumor-associated isozymes IX and XII with polyfluorinated aromatic/heterocyclic sulfonamides
Carbonic anhydrase inhibitors: Inhibition of the tumor-associated isozymes IX and XII with polyfluorinated aromatic/heterocyclic sulfonamides
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DOI：
10.1080/14756360400028101
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发表时间：
2005-06
影响因子：
5.6
通讯作者：
S. Pastoreková;D. Vullo;A. Casini;A. Scozzafava;J. Pastorek;I. Nishimori;C. Supuran
中科院分区：
文献类型：
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作者：
S. Pastoreková;D. Vullo;A. Casini;A. Scozzafava;J. Pastorek;I. Nishimori;C. Supuran
肿瘤相关的跨膜碳酸酐酶(CA，EC 4.2.1.1)同功酶IX(CA IX)和XII(CA XII)参与了缺氧性肿瘤的酸化过程，这一过程与此类肿瘤患者的不良预后和临床结局有关。这一过程可以通过用有效的磺胺/磺酸盐抑制剂抑制这些酶来逆转。研究了一系列含有2，3，5，6-四氟苯甲酰基、2，3，5，6-四氟苯磺酰基和五氟苯脲基团的芳香族/杂环磺酰胺类化合物与人同工酶Hca IX和Hca XII的催化结构域的相互作用。其中一些化合物对同工酶IX和XII表现出良好的抑制性能，其中几个亚纳摩尔抑制剂是首次检测到的。这些磺胺类药物可能成为开发基于抑制肿瘤相关CA同工酶的新型抗肿瘤药物的有价值的候选药物。
The tumor-associated transmembrane carbonic anhydrase (CA, EC 4.2.1.1) isozymes IX (CA IX) and XII (CA XII) are involved in acidification of hypoxic tumors, a process correlated with poor prognosis and clinical outcome of patients harboring such tumors. This process may be reversed by inhibiting these enzymes with potent sulfonamide/sulfamate inhibitors. A series of such aromatic/heterocyclic sulfonamides incorporating 2,3,5,6-tetrafluorobenzoyl-, 2,3,5,6-tetrafluoro- phenylsulfonyl- and pentafluorophenylureido moieties has been investigated for its interaction with the catalytic domain of the human isozymes hCA IX and hCA XII. Some of these compounds showed excellent inhibitory properties against both isozymes IX and XII, with several subnanomolar inhibitors detected for the first time. These sulfonamides may constitute valuable candidates for the development of novel antitumor therapies based on the inhibition of such tumor-associated CA isozymes.