Synthesis, in vitro acetylcholinesterase, butyrylcholinesterase activities and in silico molecular docking study of thiazole-thiourea hybrid derivatives

We have synthesized twelve thiazole-thiourea hybrid derivatives ( 1-12 ) and evaluated against acetylcholinesterase and butyrylcholinesterase enzymes. All analogues showed outstanding activities having IC 50 values ranged from 0.30 +/- 0.05 to 15.40 +/- 0.30 mu M (AChE) and 0.40 +/- 0.05 to 22.70 +/- 0.40 mu M (BuChE) as compared to standard drug Donepezil (IC 50 1 / 4 2.16 +/- 0.12 & 4.5 +/- 0.11 mu M respectively). In both cases , analogues 11 (IC 50 = 0.30 +/- 0.05 & 0.40 +/- 0.05 mu M) and analogue 12 (IC 50 = 0.80 +/- 0.05 & 1.10 +/- 0.05 mu M) withstand first and second most potent among the whole series. Structure activity relationship was carried out for all analogues which mainly depend upon number, nature, position and electron donating/withdrawing effects of the substituent/s on phenyl ring. Molecular docking study was carried out to show the binding interaction of the most potent analogue with the active site of enzyme.