Synthesis and biological evaluation of some thiazole derivatives as new cholinesterase inhibitors.
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 (1)H NMR, (13)C 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 (IC(50) = 25.5 ± 2.12 µg/mL) followed by compounds 4i (IC(50) = 38.50 ± 2.12 µg/mL), 4c (IC(50) = 58.42 ± 3.14 µg/mL) and 4g (IC(50) = 68 ± 2.12 µg/mL) when compared with eserine (IC(50) = 0.025 ± 0.01 µg/mL). Effective compounds on AChE exhibited weak inhibition on BuChE (IC(50) > 80 µg/mL). MTT assay indicated that the cytotoxic dose (IC(50) = 71.67 ± 7.63 µg/mL) of compound 4e was higher than its effective dose.
Department of Pharmaceutical Chemistry, Anadolu University, Faculty of Pharmacy, Eskişehir, Turkey.
Gülhan
G
Turan-Zitouni
Ahmet
A
Ozdemir
Zafer Asim
ZA
Kaplancikli
Mehlika Dilek
MD
Altintop
Halide Edip
HE
Temel
Gülşen Akalın
GA
Çiftçi
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*
D002800:Cholinesterase Inhibitors; D013844:Thiazoles; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase