Ondokuz Mayis University, Agricultural Faculty, Department of Agricultural Biotechnology, Samsun, Turkey.
J Enzyme Inhib Med Chem. 2012 Dec;27(6):845-8. doi: 10.3109/14756366.2011.621122. Epub 2011 Oct 14.
Carbonic anhydrase inhibitors (CAIs) are a class of pharmaceuticals used as anti-glaucoma agents, diuretics and anti-epileptics. We report here the inhibitory capacities of benzenesulphonamides, cyclitols and phenolic compounds 1-11 against three human CA isozymes (hCA I, hCA II and hCA VI) and bovine skeletal muscle carbonic anhydrase III (bCA III). The four isozymes showed quite diverse inhibition profiles with K(i) values ranging from low micromolar to millimolar concentrations against all isoenzymes. Compound 5 and 6 had more powerful inhibitory action against hCA I and very similar action against hCA II and hCA VI as compared with acetazolamide (AZA) and sulphapyridine (SPD), specific CAIs. Probably the inhibition mechanism of the tested compounds is distinct of the sulphonamides with RSO(2)NH(2) groups and similar to that of the coumarins/lacosamide, i.e. binding to a distinct part of the active site than that where sulphonamides bind. These data may lead to drug design campaigns of effective CAIs possessing a diverse inhibition mechanism compared to other sulphonamide/sulphamate inhibitors.
碳酸酐酶抑制剂（CAIs）是一类用于抗青光眼、利尿剂和抗癫痫的药物。我们在此报告苯磺酰胺、环糖醇和酚类化合物 1-11 对三种人碳酸酐酶同工酶（hCA I、hCA II 和 hCA VI）和牛骨骼肌碳酸酐酶 III（bCA III）的抑制能力。这四种同工酶表现出非常不同的抑制谱，对所有同工酶的 K(i) 值范围从低微摩尔到毫摩尔浓度。与乙酰唑胺（AZA）和磺胺嘧啶（SPD）等特异性 CAI 相比，化合物 5 和 6 对 hCA I 的抑制作用更强，对 hCA II 和 hCA VI 的作用非常相似。这些测试化合物的抑制机制可能与具有 RSO(2)NH(2)基团的磺胺类药物不同，而与香豆素/拉科酰胺的抑制机制相似，即与磺胺类药物结合的活性部位不同。这些数据可能会导致设计具有与其他磺胺类/磺酸盐抑制剂不同抑制机制的有效 CAI 的药物设计活动。
