Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.
Neurofarba Department, Section of Pharmaceutical Chemistry, Universita degli Studi di Firenze, Florence, Italy.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):1340-1345. doi: 10.1080/14756366.2022.2072837.
Carbonic anhydrases (EC 4.2.1.1) catalyse the reversible hydration of CO into bicarbonate and protons. As a hypoxia-sensitive and tumour-associated isoform, isoform CA IX, is significantly overexpressed in various malignancies, being a validated target for new anticancer/antimetastatic drugs. A multitude of studies has shown that CA IX inhibition decreases cancer cell proliferation and metastasis through pHe/pHi modulation and enhancement of ferroptosis among others. Numerous studies demonstrated increased efficacy of cytotoxic drugs combined with CA inhibitors (CAIs) in various cancer types. We tested the inhibitory effect of boric acid (BA), an inorganic Lewis acid, on CA IX as well as other isoforms (CA I, II, and XII). BA acted as a millimolar CAI, decreased proliferation of two cancer cell lines, although not strong correlations between the inhibition and effects were observed. The mechanism of antiproliferative action of BA should be investigated in more detail.
碳酸酐酶（EC 4.2.1.1）催化 CO2 的可逆水合作用，生成碳酸氢根和质子。作为一种缺氧敏感和与肿瘤相关的同工酶，同工酶 CAIX 在各种恶性肿瘤中过度表达，是新的抗癌/抗转移药物的有效靶点。大量研究表明，CAIX 抑制通过 pHe/pHi 调节和增强铁死亡等方式降低癌细胞增殖和转移。许多研究表明，在各种癌症类型中，与 CA 抑制剂（CAI）联合使用细胞毒性药物可提高疗效。我们测试了硼酸（BA），一种无机路易斯酸，对 CAIX 以及其他同工酶（CA I、II 和 XII）的抑制作用。BA 作为一种毫摩尔级的 CAI，降低了两种癌细胞系的增殖，但观察到抑制作用和效果之间没有很强的相关性。BA 的抗增殖作用机制需要更详细地研究。
