In vitro and in silico correlation of bis-thiazole based Schiff base hybrids analogues: A computational approach develop to promising acetylcholinesterase and butyrylcholinesterase inhibitors

Abstract

We have synthesized sixteen bis-thiazole based Schiff bases hybrid derivatives (1–16) and evaluated against acetylcholinesterase and butyrylcholinesterase enzymes. All analogues showed outstanding activities having IC50 values ranged from 3.57 ± 0.33 to 32.64 ± 0.70 µM (AChE) and 2.84 ± 0.11 to 34.11 ± 0.59 µM (BuChE) as compared to standard drug Donepezil (IC50 = 7.47 ± 0.35 and 7.42 ± 0.58 µM, respectively). In both cases, analogues 15 (IC50 = 3.57 ± 0.33), 10 (3.55 ± 0.51 µM) and 3 (IC50 = 3.87 ± 0.34) against AChE while analogue 4 (IC50 = 2.84 ± 0.11), 8 (IC50 = 3.48 ± 0.96) and 2 (4.02 ± 0.39 µM) against BuChE withstand most potent among the whole series. There is a relationship between structure and activity for all analogues, and the degree of this relationship varies depending on the number, nature, and position of the substituent. Docking studies were performed in order to determine how the most potent analogue interacts with the enzyme's active site.