Non-Classical Inhibition of Carbonic Anhydrase.
Non-Classical Inhibition of Carbonic Anhydrase.
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DOI：
10.3390/ijms17071150
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发表时间：
2016-07-16
影响因子：
5.6
通讯作者：
McKenna R
中科院分区：
文献类型：
--
作者：
Lomelino CL;Supuran CT;McKenna R
碳酸酐酶(CA)家族锌金属酶的特殊异构体与多种疾病有关。因此，异构体特异性碳酸酐酶抑制剂(CAI)是治疗特定疾病的主要关注焦点。经典的CAIs，主要是磺胺类化合物及其生物等位体，被认为是抗青光眼、抗癫痫、抗肥胖、抗神经病理性疼痛和抗癌的化合物。然而，许多磺胺类化合物非特异性地抑制所有CA亚型，稀释了药物的有效性，并由于靶外抑制而引起不希望看到的副作用。此外，由于磺胺过敏，一小部分但占相当大比例的普通人群无法使用磺胺类化合物进行治疗。因此，必须开发不仅具有异构体特异性而且非经典的CAI，即不以磺胺类、磺胺类或磺胺类化合物为基础。本文综述了非经典CAI的分类和基于酚类、多胺、香豆素及其衍生物的异构体特异性抑制剂的研究进展。
Specific isoforms from the carbonic anhydrase (CA) family of zinc metalloenzymes have been associated with a variety of diseases. Isoform-specific carbonic anhydrase inhibitors (CAIs) are therefore a major focus of attention for specific disease treatments. Classical CAIs, primarily sulfonamide-based compounds and their bioisosteres, are examined as antiglaucoma, antiepileptic, antiobesity, antineuropathic pain and anticancer compounds. However, many sulfonamide compounds inhibit all CA isoforms nonspecifically, diluting drug effectiveness and causing undesired side effects due to off-target inhibition. In addition, a small but significant percentage of the general population cannot be treated with sulfonamide-based compounds due to a sulfa allergy. Therefore, CAIs must be developed that are not only isoform specific, but also non-classical, i.e. not based on sulfonamides, sulfamates, or sulfamides. This review covers the classes of non-classical CAIs and the recent advances in the development of isoform-specific inhibitors based on phenols, polyamines, coumarins and their derivatives.