Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Sesto Fiorentino, Firenze, Italy.
Bioorg Med Chem Lett. 2010 Jun 15;20(12):3467-74. doi: 10.1016/j.bmcl.2010.05.009.
Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread enzymes in all organisms, catalyzing CO2 hydration to bicarbonate and protons. Their inhibition is exploited clinically for decades for various classes of diuretics and systemically acting antiglaucoma agents. In the last years novel applications of CA inhibitors (CAIs) emerged, such as topically acting antiglaucoma, anticonvulsants, antiobesity, antipain, and antitumor agents/diagnostic tools. Such CAIs target diverse isozymes of the 13 catalytically active alpha-CA isoforms present in mammals. CAs belonging to the alpha-, beta-, gamma-, delta-, and zeta-families are found in many organisms all over the phylogenetic tree, and their inhibition was studied ultimately for some pathogenic protozoa (Plasmodium falciparum), fungi (Cryptococcus neoformans, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae), and bacteria (Helicobacter pylori, Mycobacterium tuberculosis, and Brucella suis). Novel interesting chemotypes, in addition to the sulfonamide and sulfamate CAIs, such as coumarins, phenols, and fullerenes, were also reported recently, together with their mechanism of inhibition. This class of enzyme inhibitors shows promise for designing interesting pharmacological agents and understanding in detail protein-drug interactions at molecular level.
碳酸酐酶（CA，EC 4.2.1.1）是所有生物中广泛存在的酶，可催化 CO2 水合为碳酸氢盐和质子。几十年来，它们的抑制作用一直被用于各种类型的利尿剂和全身作用的抗青光眼药物的临床应用。在过去的几年中，碳酸酐酶抑制剂（CAI）出现了新的应用，如局部抗青光眼、抗惊厥、抗肥胖、抗痛和抗肿瘤药物/诊断工具。这些 CAI 针对哺乳动物中存在的 13 种催化活性α-CA 同工型中的多种同工型。属于α、β、γ、δ和ζ家族的 CA 存在于整个系统发育树中的许多生物体中，其抑制作用最终也被研究用于一些致病原生动物（恶性疟原虫）、真菌（新生隐球菌、白色念珠菌、光滑念珠菌和酿酒酵母）和细菌（幽门螺杆菌、结核分枝杆菌和布氏猪霍乱杆菌）。除了磺酰胺和磺酸盐 CAI 外，最近还报道了一些新型有趣的化学型，如香豆素、酚类和富勒烯，以及它们的抑制机制。这类酶抑制剂有望设计出有趣的药理学药物，并在分子水平上详细了解蛋白质-药物相互作用。
