New zinc binding motifs in the design of selective carbonic anhydrase inhibitors.
New zinc binding motifs in the design of selective carbonic anhydrase inhibitors.
复制标题
选择性碳酸酐酶抑制剂设计中的新锌结合基序。
DOI：
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
C. Supuran
中科院分区：
文献类型：
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作者：
J. Winum;A. Scozzafava;J. Montero;C. Supuran
碳酸氢酶(CAS，EC 4.2.1.1)是一种普遍存在的锌酶，它催化二氧化碳和碳酸氢根离子之间的相互转化，参与生理和病理过程。不同的同工酶被认为是临床应用抑制剂的重要靶点。几十年来，几种磺胺类碳酸酐酶抑制剂(CAI)被用作利尿剂、抗青光眼、抗癫痫、抗溃疡药物或治疗其他神经/神经肌肉疾病的药物，但目前几种此类药物在治疗中仍有广泛的应用，主要是作为局部作用的抗青光眼药物、抗癌或抗肥胖剂。虽然磺胺类化合物被认为是配位催化锌和设计有效的CAI的最好的部分，但近年来相关官能团如氨基磺酸、磺胺和其他被证明在选择性CAI的设计上是成功的。本文将对最近文献中报道的这些不同的锌结合功能进行综述。
The carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous zinc enzymes which catalyze a very simple physiological reaction, the interconversion between carbon dioxide and the bicarbonate ion, and are involved in physiological and pathological processes. The different isozymes have been considered as important targets for inhibitors with clinical applications. Several sulfonamide carbonic anhydrase inhibitors (CAIs) were used for decades as diuretics, anti-glaucoma, anti-epileptic, anti-ulcer agents, or as drugs for treating other neurological/neuromuscular disorders, whereas presently several such agents still find wide applications in therapy, mainly as topically acting anti-glaucoma drugs, anti-cancer, or anti-obesity agents. Although sulfonamides were considered the moiety par excellence to coordinate the catalytic zinc and for designing potent CAIs, in recent years related functional groups such as sulfamate, sulfamide and others have proven to be successful in the design of selective CAIs. The present review will deal with these different zinc binding functions recently reported in literature.