Department of Chemistry, Faculty of Science and Arts, Kırşehir Ahi Evran University, Kırşehir 40100, Turkey.
J Biochem Mol Toxicol. 2018 Sep;32(9):e22194. doi: 10.1002/jbt.22194. Epub 2018 Jul 9.
Carbonic anhydrase (CA) is an important metabolic enzyme family closely related to many physiological and pathological processes. Currently, carbonic anhydrase inhibitors are the target molecules in the treatment and diagnosis of many diseases. In present study, we investigated the inhibitory effects of some indazole molecules on the CA-I and CA-II isoenzymes isolated from human erythrocytes. We showed that human CA-I and CA-II activities were reduced by of some indazoles at low concentrations. IC values, K constants, and inhibition types for each indazole molecule were determined. The indazoles showed K constants in a range of 0.383 ± 0.021 to 2.317 ± 0.644 mM, 0.409 ± 0.083 to 3.030 ± 0.711 mM against CA-I and CA-II, respectively. Each indazole molecule exhibited a noncompetitive inhibition effect. Bromine- and chlorine-bonded indazoles were found to be more potent inhibitory effects on carbonic anhydrase isoenzymes. In conclusion, we conclude that these results may be useful in the synthesis of carbonic anhydrase inhibitors.
碳酸酐酶（CA）是一个与许多生理和病理过程密切相关的重要代谢酶家族。目前，碳酸酐酶抑制剂是许多疾病治疗和诊断的靶分子。在本研究中，我们研究了一些吲唑分子对从人红细胞中分离出的 CA-I 和 CA-II 同工酶的抑制作用。结果表明，一些吲唑类化合物在低浓度时可降低人 CA-I 和 CA-II 的活性。测定了每个吲唑分子的 IC 值、K 常数和抑制类型。吲唑类化合物对 CA-I 和 CA-II 的 K 常数分别在 0.383 ± 0.021 至 2.317 ± 0.644 mM 和 0.409 ± 0.083 至 3.030 ± 0.711 mM 范围内，每个吲唑分子均表现出非竞争性抑制作用。发现溴和氯键合的吲唑对碳酸酐酶同工酶具有更强的抑制作用。总之，我们得出结论，这些结果可能有助于碳酸酐酶抑制剂的合成。
