Ceylan Mustafa, Kocyigit Umit M, Usta Necibe Canan, Gürbüzlü Belma, Temel Yusuf, Alwasel Saleh H, Gülçin İlhami
Department of Chemistry, Faculty of Arts and Sciences, Gaziosmanpasa University, Tokat, 60250, Turkey.
Cumhuriyet University,, Vocational School of Health Services, Sivas, 58140, Turkey.
J Biochem Mol Toxicol. 2017 Apr;31(4). doi: 10.1002/jbt.21872. Epub 2016 Oct 25.
Benzothiazepine compounds have a wide range of applications such as antibacterial, antidepressants, anticonvulsants, antihypertensives, antibiotics, antifungal, hypnotic, enzyme inhibitors, antitumor, anticancer and anti-HIV agents. In this study, the synthesis of novel tetralone-based benzothiazepine derivatives (1-16) and their in vitro antibacterial activity and human carbonic anhydrase isoenzymes I and II (hCA I and II) inhibitory effects were investigated. Both isoenzymes were purified by sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography from fresh human red blood cells. All compounds demonstrated the low nanomolar inhibitory effects on both isoenzymes using esterase activity. Benzothiazepine derivative 2 demonstrated the best hCA I inhibitory effect with K value of 18.19 nM. Also, benzothiazepine derivative 7 showed the best hCA II inhibitory effect with K value of 11.31 nM. On the other hand, acetazolamide clinically used as CA inhibitor, showed K value of 19.92 nM against hCA I and 33.60 nM against hCA II, respectively.
苯并噻氮䓬类化合物有广泛的应用，如抗菌、抗抑郁、抗惊厥、抗高血压、抗生素、抗真菌、催眠、酶抑制剂、抗肿瘤、抗癌和抗HIV药物。在本研究中，研究了新型四氢萘基苯并噻氮䓬衍生物（1 - 16）的合成及其体外抗菌活性和对人碳酸酐酶同工酶I和II（hCA I和II）的抑制作用。两种同工酶均通过琼脂糖-4B-l-酪氨酸-磺胺酰胺亲和色谱法从新鲜人红细胞中纯化得到。所有化合物利用酯酶活性对两种同工酶均表现出低纳摩尔抑制作用。苯并噻氮䓬衍生物2对hCA I的抑制作用最佳，K值为18.19 nM。此外，苯并噻氮䓬衍生物7对hCA II的抑制作用最佳，K值为11.31 nM。另一方面，临床上用作碳酸酐酶抑制剂的乙酰唑胺对hCA I的K值分别为19.92 nM，对hCA II的K值为33.60 nM。
