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三氧化二羟四氟硼酸二钾,K₂[B₃O₃F₄OH],是一种强效的人源碳酸酐酶抑制剂。

Dipotassium-trioxohydroxytetrafluorotriborate, K₂[B₃O₃F₄OH], is a potent inhibitor of human carbonic anhydrases.

机构信息

Polo Scientifico, Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze , Sesto Fiorentino (Florence) , Italy .

出版信息

J Enzyme Inhib Med Chem. 2015 Apr;30(2):341-4. doi: 10.3109/14756366.2014.918610. Epub 2014 Jun 18.

Abstract

The boron heterocyclic compound dipotassium-trioxohydroxytetrafluorotriborate (K2[B3O3F4OH]) was investigated as inhibitor of the zinc enzyme, carbonic anhydrase (CA, EC 4.2.1.1). Eleven human (h) CA isoforms, hCA I-IV, VA, VI, VII, IX and XII-XIV, were included in the investigations. The anion, similar to tetraborate or phenylboronic acid, inhibited most of them. hCA III was not inhibited by K2[B3O3F4OH], whereas hCA VA, hCA VI, hCA IX and hCA XIII were inhibited in the submillimolar range, with KIs of 0.31-0.63 mM. hCA I and II (cytosolic, widespread isoforms), hCA IV (membrane-bound isoform), hCA XII (tumor-associated, transmembrane) and hCA XIV (transmembrane) were much more effectively inhibited by this anion, with inhibition constants ranging from 25 to 93 µM. hCA VII, a cytosolic enzyme present in the brain and associated to oxidative stress, was very effectively inhibited by K2[B3O3F4OH], with a KI of 8.0 µM. We propose that K2[B3O3F4OH] binds to the metal ion from the enzyme active site, coordinating to the Zn(II) ion monodentately through its B-OH functionality. We hypothesize that some of the beneficial antitumor effects reported for K2[B3O3F4OH] may be due to the inhibition of CAs present in skin tumors.

摘要

硼酸杂环化合物二钾三水合四氟硼酸氧三羟(K2[B3O3F4OH])被研究为锌酶碳酸酐酶(CA,EC 4.2.1.1)的抑制剂。十一种人(h)CA 同工酶,hCA I-IV、VA、VI、VII、IX 和 XII-XIV,均包括在研究中。该阴离子与四硼酸根或苯硼酸类似,抑制了其中大部分。hCA III 不受 K2[B3O3F4OH]抑制,而 hCA VA、hCA VI、hCA IX 和 hCA XIII 的抑制作用在亚毫摩尔范围内,KI 值为 0.31-0.63mM。hCA I 和 II(细胞质,广泛存在的同工酶)、hCA IV(膜结合同工酶)、hCA XII(与肿瘤相关,跨膜)和 hCA XIV(跨膜)受这种阴离子的抑制更为有效,抑制常数范围从 25 到 93μM。hCA VII 是一种存在于大脑中的细胞质酶,与氧化应激有关,被 K2[B3O3F4OH 非常有效地抑制,KI 值为 8.0μM。我们提出 K2[B3O3F4OH]从酶的活性部位与金属离子结合,通过其 B-OH 功能单齿配位到 Zn(II)离子。我们假设 K2[B3O3F4OH]报道的一些抗肿瘤作用可能是由于抑制了皮肤肿瘤中的 CA。

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