Department of Chemistry, Faculty of Science, Bilecik Şeyh Edebali University, Bilecik, 11230, Türkiye; Scientific Research Projects Coordinatorship, Bilecik Şeyh Edebali University, Bilecik, 11230, Türkiye.
Department of Medical Biochemistry, Faculty of Medicine, Bilecik Şeyh Edebali University, Bilecik, 11230, Türkiye.
Arch Biochem Biophys. 2024 Nov;761:110159. doi: 10.1016/j.abb.2024.110159. Epub 2024 Sep 24.
In this study, thiazole derivatives containing sulphonamide, amide, and phenyl amino groups were synthesized to protect the free amino groups of 5-methyl-4-phenyl-2-aminothiazole and 4-phenyl-2-aminothiazole. Halogenated reactions of N-protected thiazole derivatives have been investigated. LCMS, FT-IR, H NMR, and C NMR spectroscopy techniques were used to elucidate the structures of the synthesized compounds. Inhibition effects of the N-protected thiazole derivatives against human carbonic anhydrase I, II (hCA I, hCA II), and acetylcholinesterase (AChE) were investigated. The best results among the synthesized N-protected thiazole derivatives showed K values in the range of 46.85-587.53 nM against hCA I, 35.01-578.06 nM against hCA II, and in the range of 19.58-226.18 nM against AChE. Furthermore, in silico studies with the target enzyme of the thiazole derivatives (9 and 11), which showed the best results experimentally, have examined the binding interactions of the related compounds at the enzyme active site.
在这项研究中，合成了含有磺酰胺、酰胺和苯氨基的噻唑衍生物，以保护 5-甲基-4-苯基-2-氨基噻唑和 4-苯基-2-氨基噻唑中的游离氨基。研究了 N-保护噻唑衍生物的卤化反应。采用 LCMS、FT-IR、H NMR 和 C NMR 光谱技术阐明了合成化合物的结构。研究了 N-保护噻唑衍生物对人碳酸酐酶 I、II（hCA I、hCA II）和乙酰胆碱酯酶（AChE）的抑制作用。在所合成的 N-保护噻唑衍生物中，最好的结果显示对 hCA I 的 K 值范围为 46.85-587.53 nM，对 hCA II 的 K 值范围为 35.01-578.06 nM，对 AChE 的 K 值范围为 19.58-226.18 nM。此外，对实验中表现出最佳结果的噻唑衍生物（9 和 11）的靶酶进行了计算机研究，研究了相关化合物在酶活性部位的结合相互作用。
