Synthesis of N-substituted 4-phenyl-2-aminothiazole derivatives and investigation of their inhibition properties against hCA I, II, and AChE enzymes

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, 1H NMR, and 13C 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 Ki 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. [Display omitted] •N-substituted thiazole compounds were synthesized and characterised by LCMS, 1H, 13C NMR and FTIR spectroscopies.•Human carbonic anhydrase I, II (hCA I, hCA II), and acetylcholinesterase (AChE) enzymes were investigated for their inhibition properties.•In silico studies of the compounds showing the best inhibition were studied.