Synthesis and biological evaluation of some thiazole derivatives as new cholinesterase inhibitors

Article abstract of DOI:10.3109/14756366.2011.653355

In the present study, some thiazole derivatives were synthesized via the ring closure reaction of 1-[2-(2-oxobenzo[d]thiazol-3(2H)-yl)acetyl] thiosemicarbazide with various phenacyl bromides. The chemical structures of the compounds were elucidated by ¹H NMR, ¹³C NMR and mass spectral data and elemental analyses. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellman's spectrophotometric method. The compounds were also investigated for their cytotoxic properties using MTT assay. The most potent AChE inhibitor was found as compound 4e (IC50=25.5±2.12 g/mL) followed by compounds 4i (IC50=38.50±2.12 g/mL), 4c (IC50=58.42±3. 14 g/mL) and 4g (IC50=68±2.12 g/mL) when compared with eserine (IC50=0.025±0.01 g/mL). Effective compounds on AChE exhibited weak inhibition on BuChE (IC50 > 80 g/mL). MTT assay indicated that the cytotoxic dose (IC50=71.67±7.63 g/mL) of compound 4e was higher than its effective dose.