新型尿嘧啶衍生物的合成及其碳酸酐酶抑制特性
Synthesis and carbonic anhydrase inhibitory properties of novel uracil derivatives.
作者信息
Güney Murat, Çavdar Hüseyin, Şentürk Murat, Ekinci Deniz
机构信息
Ağrı İbrahim Çeçen University, Department of Chemistry, 04100 Ağrı, Turkey.
Dumlupinar University, Education Faculty, 43100 Kutahya, Turkey.
出版信息
Bioorg Med Chem Lett. 2015 Aug 15;25(16):3261-3. doi: 10.1016/j.bmcl.2015.05.073. Epub 2015 May 30.
Carbonic anhydrase (CA) inhibitors are valuable molecules based on several therapeutic applications, including antiglaucoma activity. In the present study, inhibition of two human cytosolic carbonic anhydrase isozymes I and II with some uracil derivatives (3-9) were investigated. Compounds 3-9 showed KI values in the range of 10.83-464 μM for hCA I and of 28.88-778.5 μM against hCA II, respectively. Kinetic investigations showed that similarly to classical CA inhibitors, all investigated natural compounds act as competitive inhibitors with 4-NPA as substrate. Uracil derivatives investigated here are promising agents which may be used as lead molecules in order to derivative novel carbonic anhydrase inhibitors that might be useful in medical applications.
碳酸酐酶（CA）抑制剂基于多种治疗应用，包括抗青光眼活性，是有价值的分子。在本研究中，研究了一些尿嘧啶衍生物（3 - 9）对两种人胞质碳酸酐酶同工酶I和II的抑制作用。化合物3 - 9对hCA I的KI值在10.83 - 464 μM范围内，对hCA II的KI值在28.88 - 778.5 μM范围内。动力学研究表明，与经典的CA抑制剂类似，所有研究的天然化合物以4 - NPA为底物时均作为竞争性抑制剂起作用。此处研究的尿嘧啶衍生物是有前景的药物，可作为先导分子，以衍生出可能在医学应用中有用的新型碳酸酐酶抑制剂。
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