Celik Gulsah, Khloya Poonam, Vullo Daniela, Supuran Claudiu T, Sharma Pawan K
Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.
Chemistry Department, Balıkesir University, 10145 Balıkesir, Turkey.
Bioorg Med Chem. 2014 Mar 15;22(6):1873-82. doi: 10.1016/j.bmc.2014.01.055. Epub 2014 Feb 7.
Three series of novel heterocyclic compounds (3a-3g, 4a-4g and 5a-5g) containing benzenesulfonamide moiety and incorporating a 1,2,4-triazole ring, have been synthesized and investigated as inhibitors against four isomers of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozymes hCA I and II, compounds of two series (3a-3g and 4a-4g) showed Ki values in the range of 84-868 nM and 5.6-390 nM, respectively whereas compounds of series 5a-5g were found to be poor inhibitors (Ki values exceeding 10,000 nM in some cases). Against hCA IX and XII, all the tested compounds exhibited excellent to moderate inhibitory potential with Ki values in the range of 2.8-431 nM and 1.3-63 nM, respectively. Compounds 3d, 3f and 4f exhibited excellent inhibitory potential against all of the four isozymes hCA I, II, IX and XII, even better than the standard drug acetazolamide (AZA) whereas compound of the series 5a-5g were comparatively less potent but more selective towards hCA IX and XII.
已合成了含苯磺酰胺部分并带有1,2,4-三唑环的三个系列新型杂环化合物（3a - 3g、4a - 4g和5a - 5g），并对其作为α-类碳酸酐酶（CAs，EC 4.2.1.1）四种异构体的抑制剂进行了研究，这四种异构体包括hCAs I和II（胞质、普遍存在的同工酶）以及hCAs IX和XII（跨膜、肿瘤相关同工酶）。对于人同工酶hCA I和II，两个系列的化合物（3a - 3g和4a - 4g）的Ki值分别在84 - 868 nM和5.6 - 390 nM范围内，而5a - 5g系列的化合物被发现是较差的抑制剂（在某些情况下Ki值超过10,000 nM）。对于hCA IX和XII，所有测试化合物均表现出优异至中等的抑制潜力，Ki值分别在2.8 - 431 nM和1.3 - 63 nM范围内。化合物3d、3f和4f对所有四种同工酶hCA I、II、IX和XII均表现出优异的抑制潜力，甚至优于标准药物乙酰唑胺（AZA），而5a - 5g系列的化合物效力相对较低，但对hCA IX和XII更具选择性。
