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

Abstract

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 H-1 NMR, C-13 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 mu g/mL) followed by compounds 4i (IC50 = 38.50 +/- 2.12 mu g/mL), 4c (IC50 = 58.42 +/- 3.14 mu g/mL) and 4g (IC50 = 68 +/- 2.12 mu g/mL) when compared with eserine (IC50 = 0.025 +/- 0.01 mu g/mL). Effective compounds on AChE exhibited weak inhibition on BuChE (IC50 > 80 mu g/mL). MTT assay indicated that the cytotoxic dose (IC50 = 71.67 +/- 7.63 mu g/mL) of compound 4e was higher than its effective dose.