Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, 25240, Turkey.
Department of Basic Science, Faculty of Science, Erzurum Technical University, Erzurum 25700, Turkey.
Curr Comput Aided Drug Des. 2022;18(5):381-392. doi: 10.2174/1573409918666220818114505.
Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes that contain zinc ions on the active side and convert carbon dioxide to bicarbonate in metabolism. Human CA-I and CA-II, which are the most abundant CA isozymes in erythrocytes, have been therapeutic targets in the treatment of glaucoma, hypertension, ulcer, osteoporosis, and, neurological disorders. Benzohydrazides are biologically active compounds, and their various pharmacological effects have been reported.
In light of this, the objective of this study was to investigate the in vitro effects of benzohydrazide derivatives on the activities of hCA-I and hCA-II, determine the compounds as selective inhibitors for these isoenzymes, and estimate the inhibition mechanism through molecular docking studies.
In this work, we synthesized the 10 different derivatives of benzohydrazide containing various functional group of different positions.
As a result, all benzohydrazide derivatives inhibited both isozymes in vitro and 2-amino 3- nitro benzohydrazide (10) was found to be the most efficient inhibitor of both hCA isozymes with the IC values of 0.030 and 0.047 μM, respectively. In the molecular docking studies, 3-amino 2- methyl benzohydrazide (3) had the lowest estimated free binding energies against hCA isozymes as -6.43 and -6.13 kcal/mol.
In this study, hCA-I & II isozymes were isolate from human erythrocytes. CA isozymes are one of these target enzymes. WBC hope that the benzohydrazide derivatives, can guide remedies targeting carbonic anhydrase.
碳酸酐酶（CA，EC 4.2.1.1）是一种金属酶，在活性部位含有锌离子，在代谢中将二氧化碳转化为碳酸氢盐。人红细胞中含量最丰富的同工酶 CA-I 和 CA-II 一直是治疗青光眼、高血压、溃疡、骨质疏松症和神经紊乱的治疗靶点。苯甲酰肼是具有生物活性的化合物，其各种药理作用已被报道。
有鉴于此，本研究的目的是研究苯甲酰肼衍生物对 hCA-I 和 hCA-II 活性的体外影响，确定这些化合物对这些同工酶的选择性抑制剂，并通过分子对接研究估计抑制机制。
在这项工作中，我们合成了 10 种不同位置的不同功能基团的苯甲酰肼衍生物。
所有苯甲酰肼衍生物均在体外抑制两种同工酶，而 2-氨基 3-硝基苯甲酰肼（10）对两种 hCA 同工酶的抑制作用最强，IC 值分别为 0.030 和 0.047 μM。在分子对接研究中，3-氨基 2-甲基苯甲酰肼（3）对 hCA 同工酶的估计自由结合能最低，分别为-6.43 和-6.13 kcal/mol。
在这项研究中，从人红细胞中分离出 hCA-I 和 II 同工酶。CA 同工酶是这些靶酶之一。WBC 希望苯甲酰肼衍生物可以指导针对碳酸酐酶的治疗方法。
