硫代氨基脲-苯磺酰胺衍生物作为人碳酸酐酶抑制剂的研究：合成、表征及研究。
Thiosemicarbazone-benzenesulfonamide Derivatives as Human Carbonic Anhydrases Inhibitors: Synthesis, Characterization, and Studies.
机构信息
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul, Türkiye.
Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Florence, Italy.
出版信息
Anticancer Agents Med Chem. 2024;24(9):649-667. doi: 10.2174/0118715206290722240125112447.
INTRODUCTION
Carbonic anhydrases (CAs) are widespread metalloenzymes with the core function of catalyzing the interconversion of CO and HCO -. Targeting these enzymes using selective inhibitors has emerged as a promising approach for the development of novel therapeutic agents against multiple diseases.
METHODS
A series of novel thiosemicarbazone-containing derivatives were synthesized, characterized, and tested for their inhibitory activity against pharmaceutically important human CA I (hCA I), II (hCA II), IX (hCA IX), and XII (hCA XII) using the single tail approach.
RESULTS
The compounds generally inhibited the isoenzymes at low nanomolar concentrations, with compound 6b having K values of 7.16, 0.31, 92.5, and 375 nM against hCA I, II, IX and XII, respectively. Compound 6e exhibited K values of 27.6, 0.34, 872, and 94.5 nM against hCA I, II, IX and XII, respectively.
CONCLUSION
To rationalize the inhibition data, molecular docking studies were conducted, providing insight into the binding mechanisms, molecular interactions, and selectivity of the compounds towards the isoenzymes.
简介
碳酸酐酶（CA）是广泛存在的金属酶，其核心功能是催化 CO 和 HCO - 的相互转化。使用选择性抑制剂靶向这些酶已成为开发针对多种疾病的新型治疗药物的有前途的方法。
方法
合成了一系列含有硫代缩氨基脲的新型衍生物，并使用单尾法测试了它们对具有重要药用价值的人碳酸酐酶 I（hCA I）、II（hCA II）、IX（hCA IX）和 XII（hCA XII）的抑制活性。
结果
这些化合物通常以低纳摩尔浓度抑制同工酶，化合物 6b 对 hCA I、II、IX 和 XII 的 K 值分别为 7.16、0.31、92.5 和 375 nM。化合物 6e 对 hCA I、II、IX 和 XII 的 K 值分别为 27.6、0.34、872 和 94.5 nM。
结论
为了合理化抑制数据，进行了分子对接研究，提供了对化合物与同工酶的结合机制、分子相互作用和选择性的深入了解。
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